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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:
other information
Study period:
1982-01-21 to 1982-02-04
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Significant methodological deficiency: The skin of the rabbits was abraded. The test material was in contact with abraded skin (in a series of scratches, the stratum corneum was penetrated/ abraded with a gauge needle). According to guideline OECD 402 (1987), care must be taken to avoid abrading the skin, which would alter its permeability, and the LD50 should be determined for animals treated via intact skin. Since the skin was abraded on purpose in this study and in addition the substance was clearly corrosive to skin, the mandatory prerogative of an intact skin surface is violated, and the study was therefore rated as not reliable (RL=3) for use in EU risk assessment.
Cross-reference
Reason / purpose:
reference to same study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1982
Report Date:
1982

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
, 1987-02-24
Deviations:
yes
Remarks:
, test substance purity and stability not stated, animals' skin was abraded
GLP compliance:
yes
Remarks:
FDA Good Laboratory Practice regulations & EPA Good Laboratory Practice regulations
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Sodium sulfide 60 % flake (from Lee Geiger (FMC Toxicology Department))
- Storage condition of test material: The test material was stored at room temperature.
- Other: A metal can containing beige chips
No further information on the test material was stated.

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: H.A.R.E., Hewitt, New jersey
- Weight at study initiation: Weight range of males 2.04 - 2.61 kg; weight range of females: 2.03 - 2.45 kg
- Housing: The animals were individually housed in stainless steel suspended rabbit cages. DACB cageboard bedding was used in the litter pans.
- Diet (ad libitum): Purina Laboratory Rabbit Chow # 5321
- Water (daily): Tap water
- Acclimation period: They were acclimated.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 °C - 27.8 °C
- Relative humidity: 26 % - 44 %
- Photoperiod (hrs dark / hrs light): 12/12
No further information on the test animals was stated.

Administration / exposure

Type of coverage:
occlusive
Vehicle:
physiological saline
Details on dermal exposure:
TEST SITE
- Area of exposure: Approximately twenty-four hours prior to test material administration, the trunks of ten rabbits were clipped free of hair with an electric clipper. The clipped exposure site extended from the scapulae to the pelvic girdle and encompassed approximately 10 % of the animal's body surface. The test sites were abraded with a 22-23 gauge needle just prior to dosing. This was affected by a series of horizontal scratches approximately 1-2 cm apart. The abrasions penetrated the stratum corneum but not the dermis (no bleeding).
The test material was weighed onto a 8 ply 4 X4 square inch gauze pad and moistened with the vehicle. The gauze was placed on the abraded test site.
- Type of wrap if used: The gauze pad was held in place with hypoallergenic tape. The test site was then occluded with impervious plastic sheeting. After treatment each animal was fitted with an everted plastic Elizabethan collar to prevent disturbance of the test site and possible ingestion of the test material.

REMOVAL OF TEST SUBSTANCE
- Time after start of exposure: Twenty-four hours after start of exposure
- Washing (if done): The wrapping and the gauze pads were removed and the test sites were wiped with clean gauze to remove excess test material. The Elizabethan collars remained in place until termination of the study.
No further information on the dermal exposure was stated.

Duration of exposure:
24 hours
Doses:
Dose level: 340 mg/kg (Measured individually based on body weight of each animal on the day of dosing)
No. of animals per sex per dose:
5 males / 5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were observed at 1 and 3 hours on the day of dosing and daily thereafter until day fourteen. Animals were checked for mortality twice daily. body weights were taken on days 0, 7 and 14.
- Necropsy of survivors performed: Yes
All rabbits which died during the study were necropsied. The surviving animal was killed with T-61 Euthanizing solution on day 14 and necropsied. Sections of treated skin and untreated skin were saved in 10 % buffered formalin and examined histologically.
No further information on the study design was stated.
Statistics:
No data

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
< 340 mg/kg bw
Based on:
test mat.
Remarks:
Na2S, 60 %
Remarks on result:
other: only one dose tested; significant methodological deficiency: the skin of the rabbits was abraded.
Mortality:
Six hours after dosing 4/5 male rabbits and 4/5 female rabbits were found dead. The remaining female rabbit died by Day 1.
Clinical signs:
All rabbits appeared restless and uncomfortable immediately after dosing and one rabbits vocalised 15 minutes after dosing. At the one and three hour observation all the rabbits appeared normal.
The surviving male rabbit had severe corrosion and eschar formation on its test site. It also appeared emaciated from Day 5 through Day 9. By the end of the study the rabbit began recovering as evidenced by its body weight data (Day 0: 2.04 kg; Day 7: 1.68 kg; Day 14: 2.02 kg).
Body weight:
No data
Gross pathology:
The rabbit which survived the test had black eschar formation on the test site and the underlying muscle tissue was red with fluid between the skin and muscle layers. The 9 rabbits which died during the study showed evidence of oral and nasal discharge. The skin and underlying muscles at the test sites were purple and black colour. In addition the lungs were hemorrhagic.
Other findings:
- Histopathology: Skin sections from all treated sites had undergone acute necrosis. The lesion was characterized by necrosis and loss of the epithelium and early coagulation necrosis of hair follicle epithelium and subadjacent dermal connective tissue. Deep subcutaneous oedema was present in all treated skin samples. An inflammatory response was not present in the tissues.
Sections of untreated skin were essentially within normal histological limits.

Applicant's summary and conclusion

Interpretation of results:
toxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The LD50 is less than 340 mg/kg for both male and female rabbits.
A legal classification of the test substance already exists according to Directive 67/548/EEC and 1. ATP of EC Regulation No. 1272/2008. According to these regulations the test item is classified as toxic in contact with skin. Based on the assessment of the study for REACH, classifying the test substance based on this study result is unjustified due to significant methodological deficiencies.