long chain alkyl thio carbamide metal complex

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

In-life period: 2002-05-16 to 2002-05-30

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2002

Report date:

2002

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Test material form:

liquid: viscous

Details on test material:

red viscous liquid
batch number: MRD-02-375
expiry date: 30-April-2007

Test animals

Species:

rat

Strain:

other: CD (SD) IGS

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Stone Ridge, New York
- Age at study initiation: males - 8 to 9 weeks; females - 10 to 11 weeks
- Weight at study initiation: males - 263 to 284 g; females - 216 to 239 g
- Fasting period before study: none
- Housing: singly housed in suspended stainless steel with wire mesh cages
- Diet (e.g. ad libitum): PMI certified rodent diet meal 5002, ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17.8 to 22.2
- Humidity (%): 30 to 70
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 2002-05-16 to: 2002-05-30

Administration / exposure

Type of coverage:

occlusive

Vehicle:

other: The substance was applied as supplied.

Details on dermal exposure:

TEST SITE
- Area of exposure: 5 x 10 cm
- % coverage: at least 10%
- Type of wrap if used: 6-ply gauze dressing secured with an occlusive covering held in place by Elastikon

REMOVAL OF TEST SUBSTANCE
- Washing (if done): peanut oil/paper towel
- Time after start of exposure: approx. 24 hr

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw
- Concentration (if solution): not applicable
- Constant volume or concentration used: yes
- For solids, paste formed: not applicable

VEHICLE
- Amount(s) applied (volume or weight with unit): none

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: clinical observations: 1, 2, 4 and 6 h after dosing, then daily for 14 days; weighed on days -1, 0, 7 and 14; dermal observations days 1, 4, 7, 11 and 14.
- Necropsy of survivors performed: yes, gross necropsy on day 14
- Other examinations performed: no

Statistics:

Mean and standard deviation of body weights and body weight changes

Results and discussion

Preliminary study:

none

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No deaths occurred

Clinical signs:

other: All animals were free from clinical signs of toxicity throughout the study All animal displayed increases in bodyweight during the stud y.

Gross pathology:

There were no gross abnormalities observed at postmortem.

Other findings:

Dermal irritation was noted for all animals during the study and scored according to the Draize method of scoring.
The Day 1 dermal responses could not be evaluated due to staining of the dose site by the test substance.
Erythema: day 4 - 3 animals grade 4; 1 animal grade 3; 1 animal grade 2 and 4 animals grade 1
day 7 - 9 animals grade 4
day 11 - 8 animals grade 4
day 14 - 5 animals grade 4

Oedema: day 4 - 6 animals grade 2; 3 animals grade 1
day 7 - 2 animals grade 2; 6 animals grade 1
day 11 - 6 animals grade 1
day 14 - 3 animals grade 1

Desquamation was noted for eight animals during the study (5 males; 3 females) and eschar was noted for nine (4 males; 5 females). Skin cracking was noted in 2 females on day 4 only.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

In a GLP study conducted according to OECD guideline 402, the acute dermal LD50 of EC# 457-320-2 in the rat was >2000 mg/kg bw, the limit dose. The substantial irritation produced had not been completely resolved in all animals by day 14.

Executive summary:

In a GLP study conducted according to OECD guideline 402, five male and five female rats were administered EC# 457-320-2 at 2000 mg/kg bw, the limit dose. The undiluted test material was applied to clipped skin, covering at least 10% of the body surface, under an occlusive dressing and removed after approximately 24 hours using peanut oil/paper towels. Animals were observed for up to 14 days post application. Clinical observations were made at frequent intervals during the day of application and on all subsequent days until post-mortem. Body weights were recorded pretest and on days 0, 7 and 14 and dermal observations made on days 1, 4, 7, 11 and 14.

 

All animals survived to day 14 and gained in body weight. No clinical signs of toxicity were seen in any animals. Dermal irritation was seen in all animals during the study, being first noted on Day 4 (not evaluated on Day 1 due to staining of the skin by the test material). By Day 14, the lesions had resolved in four of five males and one of five females. Irritation was scored according to the Draize method.

Erythema (grade 4) was seen in one male on Day 4, and in four, three and one male(s) on Days 7, 11 and 14 respectively. In females, grade 4 erythema was seen in two animals on Day 4 and in five, five and four animals on Days 7, 11 and 14 respectively. The highest oedema score seen, grade 2, was noted in two males on Day 4 only, whereas in females, four animals had a grade 2 lesion on Day 4 and two rats on Day 7. Other signs of local effects were eschar and desquamation, seen in animals at all time points and skin cracking, seen in two females only on Day 4.

In conclusion, the acute dermal LD50 for EC# 457-320-2 was >2000 mg/kg bw. According to EU CLP regulations, the test material would not be classified as acutely toxic by the dermal route. The local dermal toxicity had resolved completely in four males and one female by day 14, although severe erythema was still present in one male and four females at this time.