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Activity: Insecticide (pyrethroid)
Structure:

Adverse Effects:
Ataxia
Body Weight Decrease
Bone
Brain
Cholesterol
CNS
Endocrine: Breast
Endocrine: Suspected Endocrine Disruptor
Endocrine: Testes
Endocrine: Thyroid
Eye
Genotoxic / Clastogenic / Cytotoxic
Liver
Reproductive
Salivary Glands
Tremors/Convulsions
Environmental

Ataxia (click on for all fluorinated pesticides)

A 12-month feeding study in dogs fed dose (by capsule) levels of 0, 0.1, 0.5, 3.5 milligrams(mg)/kilogram (kg)/day with a no-observedeffect level (NOEL) of 0.1 mg/kg/day. The lowest-observed-effect-level (LOEL) for this study is established at 0.5 mg/kg/day based upon clinical signs of neurotoxicity ataxia, muscle tremors, convulsions.
Ref: Federal Register: March 27, 1995. Lambda-Cyhalothrin; Pesticide Tolerances. Final Rule.
http://www.fluoridealert.org/pesticides/Lambda-Cyhal.FR.Mar.27.1995.htm

Body Weight Decrease (click on for all fluorinated pesticides)

-- lambda-cyhalothrin. 13-Week feeding - rat. 00153028. NOAEL: 2.5 mg/kg/day LOAEL: 12.5 mg/kg/day reduced body weight gain and food consumption in both sexes and food efficiency in females.
-- lambda-cyhalothrin. 21-Day dermal toxicity - rat. 44333802. NOAEL: 10 mg/kg/day. LOAEL: 50 mg/kg/day. clinical signs of toxicity, decreased body weight and body weight gain.
-- lambda-cyhalothrin. 21-Day inhalation toxicity - rat. 41387702. NOAEL: 0.08 mg/kg/day. LOAEL: 0.90 mg/kg/day. clinical signs of neurotoxicity, decreased body weight gains, increased incidence of punctuate foci in cornea, slight reductions in cholesterol in females, slight changes in selected urinalysis parameters
Ref: Federal Register: September 27, 2002. Lambda-cyhalothrin; Pesticide Tolerance. Final Rule.
http://www.fluoridealert.org/pesticides/Lambda.Cyhalot.FR.Sept27.02.htm

-- A carcinogenicity study in mice fed dose levels of 0, 20, 100, or 500 ppm (0, 3, 15, or 75 mg/kg/day) in the diet for 2 years. A systemic NOEL was established at 100 ppm and systemic LOEL at 500 ppm based on decreased body weight gain in males throughout the study at 500 ppm. The Agency has determined that the chemical was not tested at a sufficiently high dose level for carcinogenicity testing in female mice. In addition, due to an equivocal finding for mammary tumors in females (1/52, 0/52, 7/52, 6/52), the Agency classified the chemical as a Group D carcinogen.
-- A developmental toxicity study in rats given gavage doses of 0, 5, 10, and 15 mg/kg/day with no developmental toxicity observed under the conditions of the study. Developmental NOEL is greater than 15 mg/ kg/day. Maternal NOEL and LOEL are established at 10 and 15 mg/kg/day, respectively. Reduced body weight and food consumption were observed during the dosing period.
-- A developmental toxicity study in rabbits given gavage doses of 0, 3, 10, and 30 mg/kg/day with no developmental toxicity observed under the conditions of the study. The maternal NOEL and LOEL are established at 10 and 30 mg/kg/day, respectively (decreased body weight gain was observed during the dosing period). The developmental NOEL is 30 mg/kg/day (highest dose tested).
-- A three-generation reproduction study in rats fed diets containing 0, 10, 30, and 100 ppm with no developmental toxicity observed at 100 ppm, highest dose tested. The maternal NOEL and LOEL for the study are established at 30 (1.5 mg/kg/day) and 100 ppm (5 mg/ kg/day), respectively, based upon decreased parental body weight gain. The reproductive NOEL and LOEL are established at 30 (1.5 mg/kg/day) and 100 ppm (5 mg/kg/day), respectively, based on decreased pup weight gain during weaning.
Ref: Federal Register: March 27, 1995. Lambda-Cyhalothrin; Pesticide Tolerances. Final Rule.
http://www.fluoridealert.org/pesticides/Lambda-Cyhal.FR.Mar.27.1995.htm

Bone (click on for all fluorinated pesticides)

Mutagenesis. 2005 May;20(3):235.
Induction of micronuclei by lambda-cyhalothrin in Wistar rat bone marrow and gut epithelial cells.
No abstract available.
Authors: Celik A, Mazmanci B, Camlica Y, Askin A, Comelekoglu U.
Note: FAN has requested a copy of this study from inter-library loan.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15886259&query_hl=30

Abstract (2005): In this study, a synthetic pyrethroid insecticide, lambda-cyhalothrin (LCT), was administered to adult female albino rats (Wistar rats) by gavage dose of 6.12, 3.06, 0.8 mg/kg b.w. repeated for 13 days at 48 h intervals. The cytotoxic and genotoxic effects of LCT were investigated in bone marrow cells, using the structural chromosomal aberration (SCA) and micronucleus (MN) test systems. Mitomycin C (MMC) was also used as positive control (2 mg/kg b.w.). All the doses of LCT increased the number of SCAs and the frequency of micronucleated erythrocytes, with respect to the control group. Only the highest dose of LCT significantly increased the MN frequency compared with control (P<0.01). It was also observed that LCT caused a significant decrease in the number of polychromatic erythrocytes compared with controls (p<0.001). These observations indicate the in vivo suspectibility of mammals to the genetic toxicity and cytotoxicity potential of LCT.
Ref: Evaluation of cytogenetic effects of lambda-cyhalothrin on Wistar rat bone marrow by gavage administration; by Ayla Çelika (a), Birgül Mazmanci, Yusuf Çamlica, Ülkü Çömelekogšlu, and Ali As¸kin
Ecotoxicology and Environmental Safety - Volume 61, Issue 1 , May 2005, Pages 128-133

Abstract (2003). In this study, the genotoxic and cytotoxic potential of lambda-cyhalothrin (LCT), a synthetic pyrethroid insecticide, was investigated in Wistar rat bone-marrow cells, using the structural chromosomal aberration (SCA) and micronucleus (MN) test systems. LCT was administrated to adult female albino rats as repeated i.p. doses of 6.12, 3.06, 0.8 mg/kg BW for 13 days at 48 h intervals. Mitomycin C (MMC) was used as a positive control (2 mg/kg BW). All the doses of LCT increased the number of structural chromosomal aberrations and the frequency of micronucleated erythrocytes, compared with the control group. It was also observed that LCT caused a significant decrease in the number of polychromatic erythrocytes. Our results demonstrate that LCT has a clastogenic/genotoxic potential as measured by the bone marrow SCA and MN tests in Wistar rats.
Ref: Cytogenetic effects of lambda-cyhalothrin on Wistar rat bone marrow; by Celik A, Mazmanci B, Camlica Y, Askin A, Comelekoglu U. Mutat Res. 2003 Aug 5;539(1-2):91-7.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12948817

Brain (click on for all fluorinated pesticides)

Abstract (2004). The peripheral effects of pyrethroids on Na(+) channels are well known but the effects on CNS neurotransmission are less known. In the present study, type I and II pyrethroids were found to affect the release of acetylcholine (ACh) from hippocampus in freely moving rats as measured by in vivo microdialysis. The basal release of ACh from the hippocampus of untreated rats was 6.6 pmol/10 microl/10 min. Allethrin had an interesting dual effect on ACh release, increasing ACh efflux (to about 300% of baseline) at the lower dose of 20 mg/kg i.p. with a peak time of 60 min and decreasing the efflux (to about 40% of baseline) at the higher dose of 60 mg/kg i.p. up to 3 h after administration. Cyhalothrin 20 and 60 mg/kg i.p. inhibited the release (to about 30% of baseline) dose-dependently, with a peak time of 50-60 min after administration. Deltamethrin 20 mg/kg i.p. increased the efflux (to about 250% of baseline) with a peak time of 30 min after administration and 60 mg/kg i.p. increased the efflux (to about 450% of baseline) and remained at a steady level during the rest of the 3 h experiment. Control vehicle injections had no effect on the efflux of ACh in any of the experiments. This is the first report, using in vivo microdialysis, that pyrethroids modulate the ACh release in the hippocampus of rat brain.
Ref: The modulatory effect of pyrethroids on acetylcholine release in the hippocampus of freely moving rats; by Hossain MM, Suzuki T, Sato I, Takewaki T, Suzuki K, Kobayashi H. Neurotoxicology. 2004 Sep;25(5):825-33.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15288513

Abstract (1990). Ca2+ + Mg2+-ATPase from microsomal fractions of rat brain was studied. The enzyme was activated by either Ca2+ or Mg2+ reaching the peak at the Ca2+ concentration of 0.3 mM. Maximal activation occurred at an ATP concentration of 5 mM with an apparent Km of 0.66 mM, a Vmax of 62.5 mumol inorganic phosphate/mg protein/hr, and a pH between 8.1 and 8.5. The enzyme was found to be ouabain insensitive but was inhibited by ruthenium red and lanthanum with I50 values of 10-5 and 10-6 M, respectively. The enzyme was highly sensitive to the actions of certain pyrethroid insecticides under in vitro conditions. The cyano-containing pyrethroids, karate and bathyroid, exerted a greater inhibitory effect on the enzyme (Ki = 1.7 and 2 muM) than the non-cyano-containing pyrethroids, permethrin and bioallethrin (Ki = 7 and 8.5 muM).
Ref: Properties of calcium, magnesium-ATPase from rat brain and its inhibition by pyrethroids; by AL-RAJHI DH. PESTIC BIOCHEM PHYSIOL; 37 (2). 1990. 116-120.

Abstract (2003). Lambda-cyhalohrin is one of synthetic pyrethroids of family of compounds with a-cyano-3-phenoxybenzyl moiety. The aim of the work was to evaluate the influence of lambda-cyhalothrin on memory processes, movement co-ordination and spontaneous movement activity in mice exposed to transient oligemic brain hypoxia in BCCA model. There were four groups of animals examined: I) sham-operated, II) after BCCA, III) sham-operated, treated with beta-cyfluthrin, and IV) after BCCA, treated with beta-cyfluthrin. Bilateral clamping of carotid arteries (BCCA) is an experimental model of transient ischemic attacks (TIAs), that occur in humans. 24 hours after the surgery, the mice had a training in the passive avoidance task. The next day the animals from group III and IV were injected with 0,1 LD50 lambda-cyhalothrin intraperitoneally. 30 minutes after administration the animals were examined in the passive avoidance task. Then, their movement co-ordination on a rota- rod was examined. After that the mice were placed in a Y maze to examine their spontaneous movement alterations and later, their spontaneous movement activity was checked. Results obtained were analysed with Anova and the post hoc tests. There is a statistically significant difference (p<0,05) in spontaneous movement activity within first 30 minutes of examination in group IV versus I and after 60 minutes in group IV vs all the others and in group II vs sham.
Conclusions: 1. Memory retention is most impaired by lambdacyhalothrin in sham-operated animals whereas BCCA-procedure protects their brains from pesticide’s toxic action.2. Lambdacyhalothrin’s effect on fresh spatial memory and spontaneous motor activity is enhanced by BCCA.
Ref: LAMBDA-CYHALOTHRIN’S INFLUENCE ON MEMORY PROCESSES, MOVEMENT CO-ORDINATION AND SPONTANEOUS MOVEMENT ACTIVITY IN MICE EXPOSED TO TRANSIENT OLIGEMIC BRAIN HYPOXIA IN BCCA MODEL; by Barbara Nieradko, Andrzej Borzecki. Toxicology Letters, Volume 144, Supplement 1, 28 September 2003, Page s147. [From Science Direct.]

Cholesterol (click on for all fluorinated pesticides)

Subchronic toxicity. A 90-day feeding study in which rats were fed doses of 0, 50, 150, and 350 ppm with a NOEL of 50 ppm and a lowest observed effect level (LOEL) of 150 ppm based on mild dose changes in hemoglobin, cholesterol, and liver weight.
Ref: Federal Register: September 25, 1997 [Page 50337-50367]. Notice of Filing of Pesticide Petitions.
http://www.fluoridealert.org/pesticides/Lambda-cyhalothrin.FR.1997.htm

CNS (click on for all fluorinated pesticides)

-- Short term toxicity. Target / critical effect: Organs Liver, CNS. Lowest relevant oral NOAEL / NOEL: 0.5 mg/kg bw/d, oral, 1 y dog.
Ref: European Commission. Review report for the active substance lambda-cyhalothrin. Finalised in the Standing Committee on Plant Health at its meeting on 19 October 2000 in view of the inclusion of lambda-cyhalothrin in Annex I of Directive 91/414/EEC. 7572/VI/97-final. 25 January 2001.
http://europa.eu.int/comm/food/fs/ph_ps/pro/eva/existing/list1-24_en.pdf

-- lambda-cyhalothrin. 21-Day inhalation toxicity - rat. 41387702. NOAEL: 0.08 mg/kg/day. LOAEL: 0.90 mg/kg/day. clinical signs of neurotoxicity, decreased body weight gains, increased incidence of punctuate foci in cornea, slight reductions in cholesterol in females, slight changes in selected urinalysis parameters
-- lambda-cyhalothrin. 1- Year oral - dog. 40027902. NOAEL: 0.1 mg/kg/day. LOAEL: 0.5 mg/kg/day. clinical signs of neurotoxicity.
-- lambda-cyhalothrin. Acute neurotoxicity - rat. 44861510. NOAEL: 10 mg/kg. LOAEL: 35 mg/kg. clinical observations indicative of neurotoxicity and changes in functional observational battery (FOB) parameters
Ref: Federal Register: September 27, 2002. Lambda-cyhalothrin; Pesticide Tolerance. Final Rule.
http://www.fluoridealert.org/pesticides/Lambda.Cyhalot.FR.Sept27.02.htm

Abstract (2003). Synthetic pyrethroids such as cyhalothrin are extensively used in agriculture for the control of a broad range of ectoparasites in farm animals. It has been suggested that type II pyrethroids might induce anxiogenic-like effects in laboratory animals. The present study was undertaken to investigate a possible anxiogenic-like outcome of cyhalothrin in rats. Adult male rats were orally dosed for 7 days with 1.0, 3.0, or 7.0 mg/kg/day of cyhalothrin, present in a commercial formulation (Grenade Coopers do Brazil S.A.). The neurobehavioral changes induced by cyhalothrin as well as those produced on corticosterone serum levels were measured 24 h after the last treatment. Picrotoxin (1.0 mg/kg) was also acutely used as a positive control for anxiety. Results showed that cyhalothrin:
(1) induced some signs and symptoms of intoxication that included salivation, tremors, and liquid feces;
(2) reduced total locomotor activity in the open-field;
(3) reduced the percentage of time spent in open-field central zones;
(4) increased immobility time in the open-field;
(5) reduced the percentage of time spent in plus-maze open arms exploration;
(6) reduced the time spent in social interactions, and
(7) increased the levels of serum corticosterone.
The behavioral changes reported for cyhalothrin (3.0 mg/kg/day) were similar of those induced by picrotoxin. The no effect level dose obtained for cyhalothrin in this study was 1.0 mg/kg/day. These results provide experimental evidence that cyhalothrin induces anxiety-like symptoms, with this effect being dose-related. Thus, anxiety must be included among the several signs and symptoms of pesticide intoxication.
Ref: Behavioral effects of type II pyrethroid cyhalothrin in rats; by Righi DA, Palermo-Neto J. Toxicol Appl Pharmacol. 2003 Sep 1;191(2):167-76.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12946652

Endocrine: Breast (click on for all fluorinated pesticides)

A carcinogenicity study in mice fed dose levels of 0, 20, 100, or 500 ppm (0, 3, 15, or 75 mg/kg/day) in the diet for 2 years. A systemic NOEL was established at 100 ppm and systemic LOEL at 500 ppm based on decreased body weight gain in males throughout the study at 500 ppm. The Agency has determined that the chemical was not tested at a sufficiently high dose level for carcinogenicity testing in female mice. In addition, due to an equivocal finding for mammary tumors in females (1/52, 0/52, 7/52, 6/52), the Agency classified the chemical as a Group D carcinogen.
Ref: Federal Register. March 27, 1995. Lambda-Cyhalothrin; Pesticide Tolerances. Final Rule.
http://www.fluoridealert.org/pesticides/Lambda-Cyhal.FR.Mar.27.1995.htm

Endocrine: Suspected Disruptor (click on for all fluorinated pesticides)

Suspected Endocrine Disruptor
Ref: PAN Pesticides Database

Endocrine: Testes (click on for all fluorinated pesticides)

AIM: To assess the effect of ICON (trade name of lambda-cyhalothrin) on sexual competence and fertility of male rats.
METHODS: Male rats were gavaged daily for 7 consecutive days with different doses of ICON (63 mg/kg and 100 mg/kg) or vehicle (distilled water). Their sexual behaviour and fertility were evaluated at different time points during treatment and post-treatment using receptive females.
RESULTS: Treatment had no effect on fertility, but sexual competence was seriously impaired: libido (assessed in terms of pre-coital sexual behaviour, and numbers of mounting, intromission and ejaculation), sexual arousability/motivation (in terms of latencies for mounting, intromission and ejaculation), sexual vigour (judged by frequencies of mounting and intromission or copulatory efficiency). In addition, ICON suppressed intromission ratio, indicating erectile dysfunction. These effects on sexual function had a rapid onset and was reversible. ICON-induced sexual dysfunction was mediated by multiple mechanisms, mainly toxicity, stress, sedation and possibly via GABA and dopaminergic systems.
CONCLUSION: Exposure to ICON may cause sexual dysfunction in male rats.
Ref: Effects of pyrethroid insecticide ICON (lambda cyhalothrin) on reproductive competence of male rats; by Ratnasooriya WD, Ratnayake SS, Jayatunga YN. Asian J Androl. 2002 Mar;4(1):35-41.
Full free text available at http://www.asiaandro.com/1008-682X/4/35.htm

Endocrine: Thyroid (click on for all fluorinated pesticides)

Limited data were available regarding endocrine effects in animals following oral exposure to pyrethroids. Serum levels of the thyroid hormones T3 and T4 were significantly decreased in mice administered fenvalerate at a dose level of 120 mg/kg/day for 15 days (Maiti and Kar 1998). Akhtar et al. (1996) reported similar effects in rats administered bifenthrin or lambda-cyhalothrin at daily oral dose levels of 0.5 mg/rat (approximately 0.75 mg/kg/day) and 0.2 mg/rat (approximately 2 mg/kg/day), respectively, for 21 days. Lambda-cyhalothrin treated rats also exhibited a significantly decreased serum T3/T4 ratio, relative to controls. In addition, both bifenthrin and lambda-cyhalothrin treatment resulted in significantly increased serum TSH levels, compared with control rats (p 39)
Ref: September 2001. Draft Toxicological Profile for Pyrethrins and Pyrethroids. US Department of Health and Human Services. Public Health Service Agency for Toxic Substances and Disease Registry.

Abstract (1996). The effects of organochlorine, organophosphorus, and pyrethroid insecticides on thyroid function were studied in rats. Young adult male albino-rats were gavaged with 0.5 milligram (mg) per rat heptachlor (76448), 0.60mg/rat benzene-hexachloride (58-89-9) (BHC), 0.06mg/rat malathion (121-75-5), 0.2mg/rat O,S-dimethyl-phosphoramidothion (10265-92-6) (Monitor), 0.5mg/rat bifenthrin (82657-04-3) (Talstar), or 0.2mg/rat lamdacyhalothrin (91465-08-6) (Karate) daily for 21 days. They were then killed and weighed. The serum was separated and analyzed for triiodothyronine (T3), thyroxine (T4), and thyrotropin (TSH) using radioimmunoassays. Except for Talstar, none of the insecticides affected body weight gain. Talstar significantly decreased body weight gain. Heptachlor and Monitor did not significantly affect serum T3, T4, and TSH concentrations. Malathion, BHC, Karate, and Talstar significantly decreased serum T3 and T4 concentrations and increased TSH concentrations. Karate significantly decreased the T43 concentration. None of the other insecticides altered the T4/T3 ratio. The authors conclude that exposure to organochlorine, organophosphorus, and pyrethroid insecticides for a relatively short time can suppress thyroid secretory activity in young adult rats. The decrease in body weight gain induced by Talstar suggests that pyrethroid insecticides can inhibit growth rate.
Ref: Insecticide-Induced Changes in Secretory Activity of the Thyroid Gland in Rats; by Akhtar N, Kayani SA, Ahmad MM, Shahab M. Journal of Applied Toxicology, Vol. 16, No. 5, pages 397-400, 26 references, 1996.

Eye (click on for all fluorinated pesticides)

21-Day inhalation toxicity - rat. 41387702. NOAEL: 0.08 mg/kg/day. LOAEL: 0.90 mg/kg/day. clinical signs of neurotoxicity, decreased body weight gains, increased incidence of punctuate foci in cornea, slight reductions in cholesterol in females, slight changes in selected urinalysis parameters
Ref: Federal Register: September 27, 2002. Lambda-cyhalothrin; Pesticide Tolerance. Final Rule.
http://www.fluoridealert.org/pesticides/Lambda.Cyhalot.FR.Sept27.02.htm

Genotoxic / Clastogenic / Cytotoxic (click on for all fluorinated pesticides)

Abstract (2005): In this study, a synthetic pyrethroid insecticide, lambda-cyhalothrin (LCT), was administered to adult female albino rats (Wistar rats) by gavage dose of 6.12, 3.06, 0.8 mg/kg b.w. repeated for 13 days at 48 h intervals. The cytotoxic and genotoxic effects of LCT were investigated in bone marrow cells, using the structural chromosomal aberration (SCA) and micronucleus (MN) test systems. Mitomycin C (MMC) was also used as positive control (2 mg/kg b.w.). All the doses of LCT increased the number of SCAs and the frequency of micronucleated erythrocytes, with respect to the control group. Only the highest dose of LCT significantly increased the MN frequency compared with control (P<0.01). It was also observed that LCT caused a significant decrease in the number of polychromatic erythrocytes compared with controls (p<0.001). These observations indicate the in vivo suspectibility of mammals to the genetic toxicity and cytotoxicity potential of LCT.
Ref: Evaluation of cytogenetic effects of lambda-cyhalothrin on Wistar rat bone marrow by gavage administration; by Ayla Çelika (a), Birgül Mazmanci, Yusuf Çamlica, Ülkü Çömelekogšlu, and Ali As¸kin
Ecotoxicology and Environmental Safety - Volume 61, Issue 1 , May 2005, Pages 128-133

Abstract (2003). In this study, the genotoxic and cytotoxic potential of lambda-cyhalothrin (LCT), a synthetic pyrethroid insecticide, was investigated in Wistar rat bone-marrow cells, using the structural chromosomal aberration (SCA) and micronucleus (MN) test systems. LCT was administrated to adult female albino rats as repeated i.p. doses of 6.12, 3.06, 0.8 mg/kg BW for 13 days at 48 h intervals. Mitomycin C (MMC) was used as a positive control (2 mg/kg BW). All the doses of LCT increased the number of structural chromosomal aberrations and the frequency of micronucleated erythrocytes, compared with the control group. It was also observed that LCT caused a significant decrease in the number of polychromatic erythrocytes. Our results demonstrate that LCT has a clastogenic/genotoxic potential as measured by the bone marrow SCA and MN tests in Wistar rats.
Ref: Cytogenetic effects of lambda-cyhalothrin on Wistar rat bone marrow; by Celik A, Mazmanci B, Camlica Y, Askin A, Comelekoglu U. Mutat Res. 2003 Aug 5;539(1-2):91-7.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12948817

Abstract (2003). Micronucleus formation in fish erythrocytes, as an indicator of chromosomal damage, has been increasingly used to detect the genotoxic potential of environmental contaminants. Nucleolar organizer regions (NORs) stained with colloidal silver techniques indicate sites of active RNA transcription. The number and size of NORs in interphase nuclei reflect cellular activities such as proliferation and differentiation of cells. In this study, nuclear (micronucleus frequency) and nucelolar (changes in quantitative characteristics of nucleoli) biomarkers were used to evaluate the functional and structural genotoxic effects of the pyrethroid insecticide lambda-cyhalothrin on Garra rufa (Pisces: Cyprinidae). The frequency of micronuclei was examined in blood smears obtained from fishes exposed to three different concentrations (0.005, 0.01, 0.05 microg/l) for a period of 36 h. Nucleolar parameters (the average number of nucleoli per cell; the volume of a single nucleolus; and the percentage of cells with heteromorphic paired nucleoli) were examined in epithelial cells obtained from the edge of caudal fins at the 90th and 180th minutes of exposure. Results of both tests demonstrated the genotoxic potential of pyrethroid lambda-cyhalothrin on G. rufa. The frequency of micronucleated erythrocytes was significantly increased while the nucleolar parameters were repressed by lambda-cyhalothrin treatment. Our results confirmed that the use of nucleolar biomarkers on fish fin cells, in addition to micronucleus test, could provide valuable information in aquatic genotoxicity studies.
Ref: Evaluation of the genotoxic potential of lambda-cyhalothrin using nuclear and nucleolar biomarkers on fish cells; by Cavas T, Ergene-Gozukara S. Mutat Res. 2003 Jan 10;534(1-2):93-9.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12504758

Abstract (1999). In order to develop experimental models able to detect genotoxic effects of pollutants in aquatic organisms, the genotoxicity of the pyrethroid lambda-cyhalothrin was studied using the micronucleus test in erythrocytes of Cheirodon interruptus interruptus. The frequency of micronuclei was examined in blood smears obtained from fishes exposed in vivo to three different concentrations (0.05; 0. 01; 0.001 ug/l) of the compound and sacrificed at nine sampling times (24, 48, 72, 96 h and 8, 12, 15, 19 and 23 days). As a positive control fishes were exposed to 5 mg/l of cyclophosphamide. Results obtained demonstrated the genotoxic effects of the pyrethroid in the experimental model employed. The variation in the micronuclei frequencies in the different sampling times could be related to the blood cell kinetics and the erythrocyte replacement. The results could be considered as a validation of the MN test in fishes for the assessment of genotoxic pollutants.
Ref: Genotoxic evaluation of the pyrethroid lambda-cyhalothrin using the micronucleus test in erythrocytes of the fish Cheirodon interruptus interruptus; by Campana MA, Panzeri AM, Moreno VJ, Dulout FN. Mutat Res. 1999 Jan 13;438(2):155-61.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10036336&dopt=Abstract

Liver (click on for all fluorinated pesticides)

-- Short term toxicity. Target / critical effect: Organs: Liver, CNS. Lowest relevant oral NOAEL / NOEL: 0.5 mg/kg bw/d, oral, 1 y dog.
Ref: European Commission. Review report for the active substance lambda-cyhalothrin. Finalised in the Standing Committee on Plant Health at its meeting on 19 October 2000 in view of the inclusion of lambda-cyhalothrin in Annex I of Directive 91/414/EEC. 7572/VI/97-final. 25 January 2001.
http://europa.eu.int/comm/food/fs/ph_ps/pro/eva/existing/list1-24_en.pdf

Reproductive / Developmental (click on for all fluorinated pesticides)

Abstract (2003). Icon is a water miscible type II synthetic pyrethroid insecticide based on active ingredient lambda cyhalothrin (10% w/w). It is used in Sri Lanka as an adulticidal indoor spray against malaria vector mosquitoes. The goal of this study was to assess the effects of Icon on pregnancy outcome of rats when exposed during early pregnancy (days 1-7). Icon was gavaged daily for 7 consecutive days in three different doses; 63, 83, or 125 mg/kg/day (active ingredient; lambda cyhalothrin; 6.3, 8.3, 12.5 mg/kg/day), respectively. Several parameters of reproduction and pre- and post-natal development were monitored. The results show that Icon is detrimental to pregnancy outcome (in terms of quantal pregnancy, number of uterine implants, implantation index and foetal deaths) but induced no detectable developmental defects. The anti-reproductive effects of Icon were mainly due to increased pre-implantation losses. Enhancement of post-implantation losses played a subsidiary role. These effects resulted from multiple mechanisms: maternal toxicity, stress, uterotropic activity and embryo-foetotoxicity. Further progesterone had a protective effect against Icon induced anti-reproductive actions. Overall, the results suggest that exposure to Icon during early gestation may result in a threat to pregnancy.
Ref: Effects of Icon, a pyrethroid insecticide on early pregnancy of rats; by Ratnasooriya WD, Ratnayake SS, Jayatunga YN. Hum Exp Toxicol. 2003 Oct;22(10):523-33.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14655718

Abstract (2002).
AIM: To assess the effect of ICON (trade name of lambda-cyhalothrin) on sexual competence and fertility of male rats.
METHODS: Male rats were gavaged daily for 7 consecutive days with different doses of ICON (63 mg/kg and 100 mg/kg) or vehicle (distilled water). Their sexual behaviour and fertility were evaluated at different time points during treatment and post-treatment using receptive females.
RESULTS: Treatment had no effect on fertility, but sexual competence was seriously impaired: libido (assessed in terms of pre-coital sexual behaviour, and numbers of mounting, intromission and ejaculation), sexual arousability/motivation (in terms of latencies for mounting, intromission and ejaculation), sexual vigour (judged by frequencies of mounting and intromission or copulatory efficiency). In addition, ICON suppressed intromission ratio, indicating erectile dysfunction. These effects on sexual function had a rapid onset and was reversible. ICON-induced sexual dysfunction was mediated by multiple mechanisms, mainly toxicity, stress, sedation and possibly via GABA and dopaminergic systems.
CONCLUSION: Exposure to ICON may cause sexual dysfunction in male rats.
Ref: Effects of pyrethroid insecticide ICON (lambda cyhalothrin) on reproductive competence of male rats; by Ratnasooriya WD, Ratnayake SS, Jayatunga YN. Asian J Androl. 2002 Mar;4(1):35-41. Full free text available at http://www.asiaandro.com/1008-682X/4/35.htm

Salivary Glands (click on for all fluorinated pesticides)

Gastrointestinal: Changes in structure or function of salivary glands.
Ref: The Registry of Toxic Effects of Chemical Substances. NIOSH.
http://www.cdc.gov/niosh/rtecs/gz12bc04.html#PCBPBS

Tremors/Convulsions (click on for all fluorinated pesticides)

A 12-month feeding study in dogs fed dose (by capsule) levels of 0, 0.1, 0.5, 3.5 milligrams(mg)/kilogram (kg)/day with a no-observedeffect level (NOEL) of 0.1 mg/kg/day. The lowest-observed-effect-level (LOEL) for this study is established at 0.5 mg/kg/day based upon clinical signs of neurotoxicity ataxia, muscle tremors, convulsions.
Ref: Federal Register: March 27, 1995. Lambda-Cyhalothrin; Pesticide Tolerances. Final Rule.
http://www.fluoridealert.org/pesticides/Lambda-Cyhal.FR.Mar.27.1995.htm