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Toxicological information

Acute Toxicity: dermal

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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1986
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Test procedure according to national standards (EPA) Comparable to OECD guideline study - the method was in principle equivalent to OECD Guideline 402.

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1992

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
not applicable
Principles of method if other than guideline:
Method: T09-02: FIFRA Pesticide Assessment Guidelines, Subdivision F, Section 81-2; "Acute Dermal Toxicity Study "TSCA Health Effects Test Guidelines; " Acute Exposure, Dermal Toxicity"
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
α,2-dichlorotoluene
EC Number:
210-258-8
EC Name:
α,2-dichlorotoluene
Cas Number:
611-19-8
Molecular formula:
C7H6Cl2
IUPAC Name:
1-chloro-2-(chloromethyl)benzene
Details on test material:
Source: Monsanto Company- Lot/Batch No.: 3168723, 2503577

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: no data
- Age at study initiation: at least 8 weeks old at study initiation
- Weight at study initiation: 2.5 kg to 3.1 kg
- Fasting period before study: no data
- Housing: individually, stainless steel cages with wire mesh bottoms
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: no data


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 60 - 70 F (ca. 16 - 21 °C)
- Humidity (%): 30 - 70%
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Type of coverage:
occlusive
Vehicle:
not specified
Details on dermal exposure:
One day before dosing, the hair of each rabbit was closely clipped from the dorsal area of the trunk with electric clipper,
so as to expose at least 10% of the body surface area. Care was taken to avoid abrading the skin.
Only animals with intact, healthy skin were used.
The test substance was applied directly onto exposed skin and spread evenly over the entire area.
Gauze was then wrapped around the animal to cover the application site.
The animal was then wrapped in an impervious plastic sleeve, designed to contain the test substance
without leakage or undue pressure. The sleeve was secured with tape and Elizabethan collars
were placed on all animals to prevent ingestion of the test substance or disruption of the wrappings.
Duration of exposure:
period of 24 h
Doses:
1000, 2000, and 4000 mg/kg bw
No. of animals per sex per dose:
5 (Fifteen male and 15 female New Zealand rabbits)
Control animals:
no
Details on study design:
Animals were observed at approximately 1, 2, and 4 hours after application and daily thereafter for fourteen days.
Gross necropsy was performed on all animals which died or were found dead during the study.
All animals surviving at the end of the observation period were sacrificed and necropsied

Results and discussion

Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LD50
Effect level:
1 700 mg/kg bw
Based on:
test mat.
95% CL:
769 - < 2 631
Sex:
female
Dose descriptor:
LD50
Effect level:
2 200 mg/kg bw
Based on:
test mat.
95% CL:
1 022 - <= 3 378
Sex:
male/female
Dose descriptor:
LD50
Effect level:
1 900 mg/kg bw
Based on:
test mat.
95% CL:
1 287 - 2 513
Mortality:
No animal death was observed at 1000 mg/kg bw during 14-day observation period. Four males and two females died at 2000 mg/kg by Day 3, and all animals were dead at 4000 mg/kg by Day 7.
Clinical signs:
The majority of animals at 2000 and 4000 mg/kg exhibited decreased activity and food consumption beginning 4 or 24 hours after administration.
Other abnormalities seen in these groups, often as antemortem signs in animals which died, included ataxia, tremors, hypopnea, hypothermia,
nasal discharge, unthrify coats and urinary and fecal staining.
Survivors (in the 2000 mg/kg group) were free of signs of systemic toxicity by Day 10.
The only systemic abnormalities seen in the 1000 mg/kg group were isolated occurrences of decreased activity
and food consumption in one or two animals through Day 7.
Most surviving animals exhibited severe dermal effects at the dose site (necrosis following by eschar formation,
fissuring and/or exfoliation of the eschar tissue) which persisted throughout the study.
Gross pathology:
Gross necropsies of animals founded dead revealed a number of abnormalities (red foci and/or discoloration of lungs, white patches of liver,
extremely large gall bladder, reddened or swollen uterus, testes found in body cavity, red walls of stomach and intestine and black foci
in stomach walls), most of which appeared to represent postmortem autolytic changes.
Observations in animals sacrificed at Day 14 confirmed the presence of dermal lesions (necrosis following by eschar formation, fissuring
and/or exfoliation of the eschar tissue), and no other abnormalities related to administration were observed.

Applicant's summary and conclusion

Interpretation of results:
harmful
Remarks:
Migrated information R21: Harmful in contact with skin / GHS Cat.4 Criteria used for interpretation of results: EU
Conclusions:
o-Chlorobenzylchloride is harmful in contact with skin.
Executive summary:

In an acute dermal toxicity study, groups of New Zealand Rabbits (5/sex) were dermally exposed to o-Chlorobenzylchloride to expose at least 10% of the body surface area at doses of 1000, 2000, and 4000 mg/kg bw. No animal death was observed at 1000 mg/kg during 14-day observation period. Four males and two females died at 2000 mg/kg bw by Day 3, and all animals were dead at 4000 mg/kg by Day 7. The majority of animals at 2000 and 4000 mg/kg bw exhibited decreased activity and food consumption beginning 4 or 24 hours after administration. Other abnormalities seen in these groups included ataxia, tremors, hypopnea, hypothermia, nasal discharge, unthrify coats and urinary and fecal staining. Survivors (in the 2000 mg/kg bw group) were free of signs of systemic toxicity by day 10. The only systemic abnormalities seen in the 1000 mg/kg bw group were isolated occurrences of decreased activity and food consumption in one or two animals through day 7. Most surviving animals exhibited severe dermal effects at the dose site which persisted throughout the study. Gross necropsies of animals founded dead revealed a number of abnormalities, most of which appeared to represent postmortem autolytic changes. Observations in animals sacrificed at day 14 confirmed the presence of dermal lesions, and no other abnormalities related to administration were observed.

 

Dermal LD50 Males      = 1700 mg/kg (95% confidence limits: 769-2631 mg/kg)

Dermal LD50 Females  = 2200 mg/kg (95% confidence limits: 1022-3378 mg/kg)

Dermal LD50 Combined = 1900 mg/kg (95% confidence limits: 1287-2513 mg/kg)