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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:
The study was performed between 6 April 1993 and 20 April 1993.
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: This study was performed according to OECD Test No. 402 Acute Dermal Toxicity and in compliance with OECD GLP standards and the United Kingdom GLP standards.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1993
Report Date:
1993

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
yes
Test type:
fixed dose procedure
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material: P5183
-Container: Clear glass jar
- Physical state: Yellow, slightly viscous liquid
- Lot/batch No.: 11/92
- Date received: 17 March 1993
- Storage condition of test material: Room temperature in the dark and dry

- Analytical purity:
3,5-diethyl-2,4-diaminotoluene 78.4%, GC (FID, area-%)
3,5-diethyl-2,6-diaminotoluene 20.0%, GC (FID, area-%)

- Impurities (identity and concentrations):
aniline, <0.02% GC (FID, area-%)
2-methyl-6-ethylaniline <0.02%, GC (FID, area-%)
2,6-diethylaniline <0.02%, GC (FID, area-%)
monoethyldiaminotoluene 0.7%, GC (FID, area-%)
3-ethyl-diaminotoluene 0.4%, GC (FID, area-%)
unknown total flow 0.1%, GC (FID, area-%)
unknown total lag 0.2% GC (FID, area-%)
water 0.04% KF (wt%)

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River (UK) Ltd., Manston, Kent, U.K.
- Identification: Each animal was given a unique number within the study by indelible ink marking on the tail and a number written on a cage card.
- Age at study initiation: Approximately 10 to 14 weeks old
- Weight at study initiation: Males (206-244 grams), Females (200-220 grams)
- Fasting period before study:
- Housing: The animals were housed in suspended polypropylene cages furnished with softwood sawdust. The animals were housed individually during the 24-hour exposure period and in groups of five, by sex, for the remainder of the study.
- Diet: ad libitum (Rat and Mouse Expanded Diet No. 1, Special Diet Services Limited, Witham, Essex, U.K.)
- Water: ad libitum
- Acclimation period: The animals were acclimated for at least five days.


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-23 °C
- Humidity (%): 46-51%
- Air changes (per hr): Approximately 15 changes per hour
- Photoperiod (hrs dark / hrs light): 12 hrs dark/ 12 hrs light


IN-LIFE DATES: From: 6 April 1993 To: 20 April 1993

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: 5 cm x 4 cm
- % coverage: Approximately 10% of the total body surface area
- Type of wrap: A piece of surgical guaze measuring 7 cm x 4 cm was placed over the treatment area and semioccluded with a piece of self-adhesive bandage (HYPERTIE). The bandage was further secured with a piece of BLENDERM wrapped around each end.


REMOVAL OF TEST SUBSTANCE
- Washing: After the 24-hour contact period, the bandage was removed and the treated skin and surrounding hair wiped with cotton wool moistened with distilled water to remove any residual test material.
- Time after start of exposure: 24 hours


TEST MATERIAL
- Amount(s) applied: 2000 mg/kg. The calculated volume of 1.97 ml/kg was determined by the specific gravity (1.017) of the test material.
- Constant volume or concentration used: yes


Duration of exposure:
24 hours
Doses:
2000 mg/kg
No. of animals per sex per dose:
5 animals/sex/dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed for deaths or overt signs of toxicity 0.5, 1, 2, and 4 hours after dosing and subsequently once daily for 14 days. Individual body weights were recorded prior to application of the test material on Day 0 and on Days 7 and 14.
- Necropsy of survivors performed: Yes, at the end of the study, the animals were killed by cervical dislocation and subjected to gross pathological examination. This consisted of an external examination and opening of the abdominal and thoracic cavities. The appearance of any macroscopic abnormalities was recorded.
Statistics:
Data evaluations included the relationship, if any, between the animals' exposure to the test material and the incidence and severity of all abnormalities including behavioral and clinical observations, gross pathological lesions, body weight changes, and any other toxicological effects.

Using the mortality data obtained, an estimate of the acute dermal median lethal dose (LD50) of the test material was made.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
approximate LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
No deaths occurred.
Clinical signs:
All animals were lethargic with hunched posture and ptosis on day 1, following exposure. On day 2, all animals were lethargic and had a hunched posture. On day 3, four male rats and two female rats were lethargic, and all rats had hunched posture. On day 4, five male rats and two female rats had hunched posture. From day 5 until study termination on day 14, no signs of toxicity were observed.
Body weight:
All animals showed expected gain in body weight during the study. Mean body weight gains for males during weeks 1 and 2 were 36 +/ 4 grams and 54 +/- 18 grams. Mean female body weight gains during weeks 1 and 2 were 17 +/- 6 grams and 22 +/- 4 grams.
Gross pathology:
No abnormalities were noted at necropsy.
Other findings:
No signs of skin irritation were noted during the study. Green colored staining of the fur was observed with all animals on day 1 after initiation of exposure. No further signs were observed from day 2 through day 14.

Applicant's summary and conclusion

Conclusions:
The dermal LD50 was >2000 mg/kg body weight.
Executive summary:

The acute dermal median LD50 of the test material in the Sprague-Dawley strain was to be greater than 2000 mg/kg body weight.