|
Return to
Index Page
Adverse Effects
This is a "doc" document available at http://ecb.jrc.it/classlab/agenda/14604r2_ag_Health_0305.htm
Clodinafop-propargyl (P623/NL)
Proposal for specific concentration limits for the R43 classification
of
The Netherlands, March 2005
During the TC-C&L meeting of March 2005, it was agreed to classify
clodinafop-propargyl with R43. Further, the Netherlands proposed
a specific concentration limit of 0.001% according to the report
of the sensitisation working expert group (ECBI/81/02 Rev. 2).
Available sensitisation study with clodinafop-propargyl:
Characteristics
| reference |
: |
Schneider,
1987 |
exposure |
: |
9 intradermal
inductions, 1 intradermal challenge and 1 topical challenge
(occlusive, 24 hours) |
| type of
study |
: |
skin sensitisation
study (Optimization test) |
doses |
: |
0.1% for
intradermal induction and challenge, 5% for topical challenge
|
| year of
execution |
: |
1987 |
vehicle |
: |
intradermal
injections: 10% ethanol and 90% physiological saline, last six
inductions with complete Bacto adjuvant (1:1); topical application:
vaseline. |
| test substance |
: |
CGA 184927
tech., clodinafop-propargyl, batch no. P. 612003, purity 93.7% |
GLP statement |
: |
yes |
| route |
: |
dermal |
guideline |
: |
performed
in accordance with OECD 406 |
| species |
: |
guinea
pig, Pirbright White strain (Tif:DHP) |
acceptability |
: |
acceptable |
| group size |
: |
10/sex/group |
Effect |
: |
sensitising
to skin |
Study design
The study was performed in accordance with OECD 406 of 1981, which
was prevailing at the time of the study. The test substance concentration
for topical challenge was based on a pre-test in which separate
animals were treated topically with 1, 5, 10 and 30% of the test
material in vaseline. No irritation was observed at 1 and 5%.
Results
Skin reactions were observed in all test substance treated animals
in response to the intradermal 0.1% test substance challenge concentration
and in response to the 5% topical challenge concentration. No skin
reactions were evident after the challenge exposure in the control
animals.
Acceptability
The study was performed in accordance with the OECD guideline of
1981. According to the current OECD 406 guideline, a maximization
test would be preferred. According to the principles of an optimization
test, as described in OECD 406 of 1981, animals should be subjected
to two challenge exposures by intradermal injection. In the current
study, animals were challenged by a single intradermal injection
14 days after the last induction and by topical exposure 24 days
after the last induction. However, based on the results observed
in control and test substance treated animals after both challenges,
the study is considered acceptable.
Conclusions
In an optimization test, clodinafop-propargyl was sensitising to
the skin of guinea pig. The concentration
used for repeated intradermal induction was 0.1% and this resulted
in 100% sensitisation using dermal or intradermal challenge.
No information is provided by the sensitisation expert group for
potency categorisation based on the optimization test. However,
the induction concentration of 0.1% is equal to or below the concentration
needed to grade a substance as an extreme sensitizer in all other
sensitisation tests for which a proposal for potency categorisation
was provided in ECBI/81/02 Rev.2. Therefore, categorisation
of clodinafop-propargyl as an extreme sensitizer is proposed. This
results in a specific concentration limit of 0.001% for R43.
|
