Registration Dossier

Toxicological information

Acute Toxicity: dermal

Currently viewing:

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
04.03.1985 to 02.04.1985
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1985
Report Date:
1985

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
no
Remarks:
Study was conducted prior to GLP.
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Hazleton-Dutchland Laboratory animals
- Age at study initiation: 8 weeks
- Weight at study initiation: Males: 2.2-2.7 kg. Females: 2.5-2.7 kg
- Fasting period before study: No
- Housing: Individually, in suspended stainless steel cages
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: 15 days


ENVIRONMENTAL CONDITIONS
- Temperature (°F): 60-70
- Humidity (%): 30-70
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: 19.03.85 To: 02.04.85

Administration / exposure

Type of coverage:
occlusive
Vehicle:
other: aqueous solution, administered undiluted.
Details on dermal exposure:
TEST SITE
- Area of exposure: Dorsal area of the trunk
- % coverage: 10% of body surface area
- Type of wrap if used: Impervious plastic sleeve


REMOVAL OF TEST SUBSTANCE
- Washing (if done): test sites wiped free of excess test substance
- Time after start of exposure: 24 hours


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 3.8 ml/kg
Duration of exposure:
24 hours
Doses:
5000 mg/kg bw
No. of animals per sex per dose:
Five
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Viability: Twice daily. Clinical signs: 1, 2, and 4 hours after dosing and then daily for 14 days. Body weights: Pretest, immediately prior to dosing and days 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: Macroscopic examination of all animals.
Statistics:
None

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Remarks on result:
other: Presumed equivalent to 3505 mg active acid/kg bw
Mortality:
One female died on Day 13. However, macroscopic examination revealed signs of intestinal disease that was not thought to be related to the test substance. All other animals survived to the end of the observation period.
Clinical signs:
In all surviving animals there were some occurrences of oral and nasal discharge. Most animals had severe dermal effects at the dose site (necrosis followed by eschar formation and/or exfoliation of the eschar tissue), which persisted throughout the observation period.
Body weight:
Most animals had slight weight losses at Days 7 and/or 14.
Gross pathology:
The female that was found dead had gross abnormalities suggestive of mucoid enteritis. Apart from the presence of dermal lesions, there were no abnormal findings in the other animals.
Other findings:
None reported.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
In a well-conducted acute dermal toxicity limit test, conducted according to a protocol that was similar to OECD 402, but not to GLP, the dermal LD50 for Dequest 2016 was >5000 mg/kg bw (IUCLID 4 reviewer comment: presumed equivalent to 3505 mg active acid/kg bw) in the rabbit.
Executive summary:

In a well-conducted acute dermal toxicity limit test, conducted according to a protocol that was similar to OECD 402, but not to GLP, 5000 mg/kg bw of Dequest 2016 was applied to the skin of New Zealand white rabbits (5/sex) under an occlusive dressing, for 24 hours. After the 24 hour exposure period excess test substance was wiped off the test site. Animals were then observed for 14 days for signs of toxicity, and body weights were measured prior to dosing and on days 7 and 14. All animals were examined macroscopically. One female died on Day 13. However, macroscopic examination revealed signs of intestinal disease that was not thought to be related to the test substance. All other animals survived to the end of the observation period. In all surviving animals there were some occurrences of oral and nasal discharge. Most animals had severe dermal effects at the dose site (necrosis followed by eschar formation and/or exfoliation of the eschar tissue), which persisted throughout the observation period. Most animals had slight weight losses at Days 7 and/or 14. The female that was found dead had gross abnormalities suggestive of mucoid enteritis. Apart from the presence of dermal lesions, there were no abnormal findings in the other animals. The LD50 was determined to be >5000 mg/kg bw.