CAS No. 177406-68-7

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ACTIVITY: Fungicide (Carbamate)

Name: [[isopropyl[(S)-1-[(R)-1-(6-fluoro-1,3-benzothiazol-2-yl)ethyl]carbamoyl-2-methylpropyl]carbamate]

Structure for Benthiavalicarb-isopropyl

Structure for Benthiavalicarb:

Adverse Effects:

Cancer: Uterine, Liver, Thyroid
Endocrine: Uterus

Information for Benthiavalicarb (413615-35-7):
Regulatory Information
(only comprehensive for the US)
US EPA Registered: Yes


US Maximum Residue Tolerance Levels: US
• imported grapes
• grape processed commodities juice and wine
• imported tomato
• tomato processed commodities
• tomato paste
Other Information
Molecular Formula: C15H18FN3O3S
Manufacturer: Kumiai Chemicals Industry Co Ltd
Entry Date: 2002
Other Names: KIF 230
Of special interest:

PAN Data

2004: First evaluation for UK approval (COPR) of Benthiavalicarb-Isopropyl (KIF-230) as an agricultural fungicide in the product ‘KIF 230 + Mancozeb’ for use on potatoes.  ACP 6 (306/2004) Benthiavalicarb-isopropyl (code name KIF 230) is a new valinamide fungicide. A commercial level of approval is being requested for the use of ‘KIF-230+mancozeb’, a wettable granule formulation containing 17.5 g/kg benthiavalicarb-isopropyl and 700 g/kg mancozeb, for use on all varieties of potatoes including early and maincrop varieties and seed crops.
Ref: Advisory Committee on Pesticides (ACP) Draft Agenda 306th Meeting 18 March 2004.
Jan 10, 2003 - A dossier for the active substance benthiavalicarb was submitted by Kumiai Chemicals Industry Co Ltd to the authorities of Belgium on 19 April 2002. Official Journal of the European Communities. 
See also Benthiavalicarb
2001: Kumiai Chemical Industry has signed a license option agreement with Bayer for its novel fungicide KIF-230 (proposed ISO name: benthiavalicarb). Kumiai is targeting an international launch of a range of proprietary benthiavalicarb mixtures in 2003 with substantial sales projected. Bayer will examine the commercialisation of its own specific benthiavalicarb formulations. Benthiavalicarb is an amino acid amide carbonate that was discovered at K-I Laboratories, a joint venture between Kumiai Chemical and Ihara Chemical Industry. The fungicide displays very good efficacy against downy mildew and other diseases in grapes, potatoes and vegetables at doses of less than 100g ai per hectare. Kumiai Chemical plans to make registration submissions over the coming year in Japan, Europe, Latin America and elsewhere. Ihara Chemical will  produce the fungicide.
Ref: Crop Protection Monthly (UK). 8 April 2001 - Issue No 137

U.S. Federal Register
Date Docket Identification No. Details
September 1, 2006 EPA-HQ-OPP-2005-0035 K-I Chemical U.S.A., Inc. Pesticide Tolerance. FINAL RULE.
in or on the raw agricultural commodity
-- imported grapes at 0.5 ppm
-- grape processed commodities juice and wine at 0.5 ppm
-- imported tomato at 0.5 ppm
-- tomato processed commodities at 0.5 ppm
-- tomato paste at 1.5 ppm
March 9, 2005 OPP-2005-0035

K-I Chemical U.S.A. Petition for the Establishment of Tolerances on Imported Grapes and Tomatoes.
Pesticide petition PP 3E6545. According to this petition:
There are no registered uses of benthiavalicarb-isopropyl in the U.S. and no other
tolerance petitions have been submitted to EPA for this active
ingredient. Dietary exposure is limited in the U.S. to residues in/on
imported grapes and tomatoes and their processed components

Tolerances requested:
in or on the raw IMPORTED agricultural commodities:
grapes 0.5
grape processed commodities juice 0.5
grape processed commodities wine 0.5
tomato 0.5
tomato processed commodities 0.5
tomato paste 1.5

Reproductive and developmental toxicity
In a 2-generation reproduction study in Sprague Dawley rats receiving 0, 100, 1,000 or 10,000 ppm benthiavalicarb-isopropyl in the diet, the parental no observed adverse effect level (NOAEL) was 100 ppm based on hepatocyte hypertrophy at the next higher dose level. The reproductive NOAEL was 10,000 ppm.
.....• In a developmental toxicity study in New Zealand White rabbits receiving 0, 10, 20 or 40 mg/kg/day benthiavalicarb-isopropyl from day 6 to 28 of gestation, the maternal NOAEL was 20 mg/kg/day based on abortion and increased liver weights at the 40 mg/kg/day dose. The
developmental NOAEL was 20 mg/kg/day based on
increased incidence of small fetus and delayed ossification of the hindlimb talus at 40 mg/kg/ day.
In a developmental toxicity study in Sprague Dawley rats receiving 0, 10, 100 or 1,000 mg/kg/day from day 7 to day 19 of gestation, the maternal NOAEL was 10 mg/kg/day based on elevated liver and adrenal weights at 100 mg/kg/day. The NOAEL for developmental toxicity was 1,000 mg/kg/day.

Subchronic toxicity.
• In the 13-week feeding study with mice, the dose levels were 0, 50, 200, 7,000, or 20,000 ppm. The NOAEL was 200 ppm (equivalent to 33.0 mg/kg/day and 45.2 mg/kg/day in males and females, respectively, based on systemic toxicity of decreased body weights, anemias, and
generalized liver toxicity at 7,000 ppm.
In the 3 month dog feeding study the dose levels were 0, 40, 200, or 1,000 mg/kg/day. The NOAEL was 40 mg/kg/day based on hematological and clinical chemistry changes, organ weight changes and the findings of hepatocyte hypertrophy and pigmentation in the spleen at 200 mg/kg/day.

Chronic toxicity.
.....• In a chronic/oncogenicity study Fisher rats received 0, 50, 200, 5,000, or 10,000 ppm of benthiavalicarb- isopropyl for up to 104 weeks. The NOAEL was 200 ppm (9.9 mg/kg/day and 12.5 mg/kg/day in males and females respectively), based on a variety of toxic effects, primarily in the liver and kidney, and adenocarcinomas of the uterus at 5,000 ppm.
In an oncogenicity study in mice, the dietary doses were 0, 20, 100, 2,500 or 5,000 ppm. The NOAEL was 100 ppm (13.7 mg/kg/day and 18.6 mg/kg/day in males and females, respectively) based on a variety of toxic effects, primarily in the liver and kidney, and hepatocellular blastoma and carcinoma at 2,500 ppm.
In a 52-week study with Beagle dogs, the dietary dose levels were 0, 4, 40, or 400 mg/kg/day. The NOAEL was 40 mg/kg/day based on increased liver weights in males and females at 400 mg/kg/day.
Numerous supplemental mechanistic studies in the rodent were carried out to further elucidate the mechanisms involved in tumor formation in the lifetime rodent studies. These studies indicated that
benthiavalicarb-isopropyl behaves like a promotor following initiation with diethylnitrosamine (DEN), and does not have initiating activity. The compound did not cause oxidative damage in studies on rat or mouse liver, was a slight enzyme inducer, and did not cause hepatocyte proliferation.

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