Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
01.08.1991 to 10.10.1991
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1992
Report Date:
1992

Materials and methods

Test guidelineopen allclose all
Qualifier:
equivalent or similar to
Guideline:
other: TSCA
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

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 research Products, Inc., Denver, PA.
- Age at study initiation: 12 to 18 weeks
- Weight at study initiation: 2.1 to 3.2 kg
- Fasting period before study: No
- Housing: Individually in cages with wire floors
- Diet: Ad libitum
- Water: Ad libitum
- Acclimation period: At least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18.9-22.2
- Humidity (%): 33-60%
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 01.08.1991 to 10.10.1991

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: Dorsal trunk
- % coverage: Not stated - "as large an area as possible" was treated.
- Type of wrap if used: A double layer of gauze sheeting was wrapped around the trunk and secured with adhesive tape. Polyethylene sheeting was then wrapped around the trunk over the gauze. The sheeting was protected with bandaging tape.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): No

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): volume varied according to the weight of the rabbits.
Duration of exposure:
24 hours
Doses:
2, 4 and 8 g/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: Animals were observed frequently for signs of toxicity on the first day of the test, and twice daily thereafter. Weights were recorded on the day of dosing and at 7 and 14 days after dosing and death.
- Necropsy of survivors performed: yes, after 14 days, all survivors were sacrificed. Microscopic examinations were performed on selected tissues from several rabbits.
Statistics:
The LD50 was calculated by the Moving Average Method.

Results and discussion

Effect levelsopen allclose all
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
6 730 mg/kg bw
Based on:
test mat.
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 8 000 mg/kg bw
Based on:
test mat.
Mortality:
One of the female rabbits died following a dose of 8 g/kg bw, but there were no deaths following 4 and 2 g/kg bw. Three, one and no male animals died at 8, 4 and 2 g/kg bw. Deaths occurred on days three to six.
Clinical signs:
Dermal reactions included erythema, oedema, necrosis, fissuring, desquamation and alopecia (signs of skin irritation at all doses in both sexes). Signs of toxicity included sluggishness, an unsteady gait, laboured breathing, forelimb paralysis (one male that died), hindlimb paresis (reversible weakness to temporary loss of ability to stand), nephrititis, slight wetness of the perinasal fur, head with swaying motion. Recovery of survivors was 2-14 days.
Body weight:
Weight loss was observed, so animals with emaciation.
Gross pathology:
Necropsy of the animals that died revealed hemorrhaged intestines (one animal) and a small amount of blood in the urine of one. In survivors there were instances of dark/bright red lungs, intestines of one animal were partially filled with gas, an enlarged spleen and a raised tan nodule on one kidney.
Other findings:
Selected tissues from six males and six females were examined microscopically. Lesions observed included interstitial nephritis and calculi in the urinary bladder. These findings were considered to be incidental and not related to the treatment. There were no lesions apparent in the examined spinal cords or sciatic nerves of any animal.

Any other information on results incl. tables

Table 1 Summary of acute dermal study results

Dose (g/kg bw)  Dead/dosed  Mean weight (g ± SD)         Signs of toxicity
     0 days  7 days  14 days  
 8.0 (males)  3/5  2364 ± 116  2228 ± 97  2448 ± 86  Sluggishness in 1 at day 1, emaciation of 1 at death. Weight loss evident in survivors at 7 days with recovery by 14 days.
 4.0 (males)  1/5  2534± 153  2360 ± 89  2496 ± 164 Sluggishness in 1, unsteady gait in 2 at day 1; laboured breathing and forelimb paralysis in 1 that died at 1 day; hindlimb paresis in 3 at 2 days, emaciation of 1 at death. Partial recovery of 2 from paresis at day 7. Complete recovery of 3 at 2 to 14 days.  
 2.0 (males)  0/5  2604± 202  2444± 166  2651± 160 Iritis in 1 at day 1. Recovery at 2 days. Emaciation of 1 at 6 days, paresis (weakness) in all limbs of 1 at 7 days. Complete recovery at 14 days.  
 8.0 (females)  1/5  2778± 63  2368± 254  2551± 277  Sluggishness in 2, unsteady gait in 1, laboured breathing in 1, slight wetness of perinasal fur of 1 at day 1; paresis (difficulty in standing) in 2 survivors at 1 or 7 days; emaciation of 3 at death or 7 days. Death of 1 at 4 days. All survivors recovered at 7 to 14 days.
 4.0 (females)  0/5  2415± 151  2342± 180  2533± 192  Sluggishness and slight swaying motion of head in 1 at day 1. Recovery at 14 days.
 2.0 (females)  0/5  2277± 85 2323± 69   2575± 110  None noted.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
In an acute dermal toxicity study conducted using a protocol comparable to OECD 402, and in compliance with GLP (reliability score 1) the LD50 for male rabbits was 6730 mg/kg bw, and for females was at least 8000 mg/kg bw. Dermal reactions included erythema, oedema, necrosis, fissuring, desquamation and alopecia (signs of skin irritation at all doses in both sexes). Signs of toxicity included sluggishness, an unsteady gait, laboured breathing, forelimb paralysis (one male that died), hindlimb paresis (reversible weakness to temporary loss of ability to stand), nephrititis, slight wetness of the perinasal fur, head with swaying motion. Recovery of survivors was 2-14 days. There were no treatment-related microscopic findings.