Hydrocarbons, C10, aromatics, >1% naphthalene

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From November 14, 1994 To November 29, 1994

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Acceptable, well-documented study report in agreement with OECD test guideline 402-GLP

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1995

Report date:

1995

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

GLP compliance:

yes

Test type:

standard acute method

Test material

Test material information

Constituent 1

Reference substance name:

Hydrocarbons, C10, aromatics, >1% naphthalene

EC Number:

919-284-0

Cas Number:

Not applicable

Molecular formula:

None available - not a single isomer - see remarks

IUPAC Name:

Hydrocarbons, C10, aromatics, >1% naphthalene

Details on test material:

- Name of test material (as cited in study report): MRD-94-953
- Physical state: Colorless liquid
- Analytical purity: assume 100% purity
- Stability under test conditions: Not documented. Material stable under normal conditions
- Storage condition of test material: room temperature

Test animals

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: HRP Inc., Denver, PA
- Age at study initiation: Males: approximately 13 weeks; females: approximately 10 weeks
- Weight at study initiation: 2.05-2.43kg
- Housing: individually
- Diet (e.g. ad libitum): Based on recommendations of the animal supplier, in an effort to improve the health of the animals, the amount of feed administered to the animals was limited on a daily basis.
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 8 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18.3-21.1 °C
- Humidity (%): 40 to 60 percent relative humidity
- Photoperiod (hrs dark / hrs light): 12hrs dark /12 hrs light


IN-LIFE DATES: From: November 15, 1994 To: November 29, 1994

Administration / exposure

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: dorsal surface from the shoulder region to the lumbar region
- % coverage: at least 10% of the body surface
- Type of wrap if used: the gauze patch was secured to the trunk of the animal with a plastic sleeve


REMOVAL OF TEST SUBSTANCE
- Washing (if done): reverse osmosis water and paper towels
- Time after start of exposure: approximately 24 hours


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000mg/kg

Duration of exposure:

24 hours

Doses:

2000mg/kg dose

No. of animals per sex per dose:

5 males; 5 females (nulliparous and non-pregnant)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical observations were made at 2 and 4 hours after dosing, and daily thereafter for a total of 14 days.
Body weights were recorded once prior to dosing initiation; on Days 0, 7, 14; and on the day of sacrifice. Dermal responses were evaluated on Day 1 (30 to 60 minutes after patch removal) and on Days 3, 7, and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, organ weights, histopathology, other: Clinical observations were made as to the nature, onset, severity, and duration of toxicological signs; Dermal responses were evaluated according to the Draize method of scoring.

Statistics:

Statistical analyses included means and standard deviations of body weights and body weight change by group and sex.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Remarks on result:

other: no evidence of systemic toxicity under the conditions of this study at this dose

Clinical signs:

other: All animals survived to study termination. There were no treatment-related clinical signs. At the 2 and 4 hour observations, one female had mucoidal stool. At the Day 1 observation, one female was noted with a reddened nictitating membrane. These find

Gross pathology:

At the postmortem examination, four males and two females were noted with desquamation and/or eschar on the dose site which was consistent with their inlife dermal observations. The remaining male and three females had no macroscopic abnormalities.

Other findings:

Topical application of the test material elicited dermal irritation in all animals. At the Day 1 observation, eight animals had well-defined erythema and two animals had moderate/severe erythema. At the Day 3 observation, five animals had well-defined erythema, two animals had moderate/severe erythema, and one animal had severe erythema. At the Day 7 observation, four animals had very slight erythema, three animals had well-defined erythema, and one animal had severe erythema. On Day 14, three animals had very slight erythema, one animal had well-defined erythema, and four animals had severe erythema/slight eschar formation.

Edema was observed in all animals. At the Day 1 observation, one animal had very slight edema, one animal had slight edema, and eight animals had moderate edema. At the Day 3 observations, one animal had very slight edema and four animals had slight edema. Edema was not observed in any animal on Day 7. At the Day 14 observation, one animal had slight edema.

Other dermal observations included atonia, cracking, desquamation, eschar, exfoliation, fissuring, and leathery texture of the dose site.

Severe dermal irritation from mechanical damage at undamming was observed in all ten animals at sleeve removal and in nine animals at the Day 1 observation. This irritation was not scored.

Applicant's summary and conclusion

Interpretation of results:

other: Not classified

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of this study, the dermal LD50 for MRD-94-953 is greater than 2000 mg/kg. Classification as an acute dermal toxicant is not warranted under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP) or under Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations.

Executive summary:

The acute toxicity of MRD-94-953 was evaluated following its application to the clipped backs of ten New Zealand White rabbits.  A single dose of 2000 mg/kg of the test material was applied to not less than 10% of the body surface, covered with a gauze patch, and secured with non-irritating tape and a plastic sleeve.  Clinical observations were performed 2 and 4 hours after dosing, and once per day thereafter for a total of 14 days.  Dermal responses were evaluated on Days 1, 3, 7, and 14 according to the Draize method of scoring.  Body weights were recorded the day prior to dosing, the day of dosing (Day 0), and on Days 7 and 14.  Application of MRD-94-953 at a dose level of 2000 mg/kg showed no evidence of systemic toxicity under the conditions of this study and all animals survived to study termination.  There were no treatment-related clinical signs.  Dermal irritation was the most significant finding and was observed in the majority of animals throughout the study. 

 

Based on the results of this study, the dermal LD₅₀ for MRD-94-953  is greater than 2000 mg/kg in the rabbit. Classification as an acute dermal toxicant is not warranted under the new Regulation (EC) 1272/2008 on classification, labelling and packaging of substances and mixtures (CLP) or under Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations.