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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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: This study is classified as reliable without restriction because it was conducted in accordance with OECD 402 guideline and was GLP compliant.
Justification for type of information:
A discussion and report on the read across strategy is given as an attachment in Section 13.
Cross-reference
Reason / purpose:
read-across: supporting information
Reference
Endpoint:
acute toxicity: dermal
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: This study is classified as reliable without restriction because it was conducted in accordance with OECD 402 guideline and was GLP compliant.
Justification for type of information:
A discussion and report on the read across strategy is given as an attachment in Section 13.
Reason / purpose:
read-across source
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Ray Nichols Rabbitry, Lumberton, Texas
- Weight at study initiation: Weights recorded on day -1
- Fasting period before study: No
- Housing: Individually caged
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: 18 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.6 to 23.9
- Humidity (%): 36 to 71%
- Photoperiod (hrs dark / hrs light): 12 dark/12 light

IN-LIFE DATES: From: 1981-06-25 To: 1981-07-28
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: Not reported
- % coverage: Not reported
- Type of wrap if used: Surgical gauze secured with tape and covered with aluminium foil and an overwrap of an elastic Ace bandage

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Yes
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2.0 g/kg
- Constant volume or concentration used: No. Specific amount of test material administered was calculated using fasted body weights on day -1 and specific gravity of 0.673 for Neodene 6.
- Other: Each animal tested had two application sites (1 intact and 1 abraded)
Duration of exposure:
24 hours
Doses:
2000 mg/kg Neodene 6, 2 mL/kg deionised water (control)
No. of animals per sex per dose:
4
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations made at 1, 2, 4, and 6 hours following application, at 24 hours and twice daily thereafter until termination of study on day 14.
- Necropsy of survivors performed: Yes
- Other examinations performed: Clinical signs, body weight
Statistics:
Statistical analysis for significance of body weight changes included the calculation of the mean and standard error. Determination of the significance of body weight changes on days 7 and 14 compared to controls was made using an independent T-test. A probability level of 0.05 was used as criterion for significance. No information reported on method used to calculate LD50.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
No deaths were reported in this study.
Clinical signs:
No clinical signs of toxicity associated with administration of the test material were reported.
Body weight:
No significant reduction in body weight gain occurred in the test animals on either day 7 or day 14 as compared to the control group.
Gross pathology:
The only significant findings were related to the exposure sites and included white, crusty material on the skin and fur, alopecia, abrasions, and focal reddened areas.
Other findings:
Slight erythema and oedema were observed in all animals treated with Neodene 6 24 hours post-application. The average erythema and oedema scores for abraded skin animals were 0.8 and 1.4, respectively. The average erythema and oedema scores for intact skin animals were 0.5 and 1.2, respectively. All reported Draize scores were 0.0 on day 14 for all animals.

No tables included based on negative results.

Interpretation of results:
other: Not classified
Remarks:
Not classified because LD50 is greater than the requirements for a Category 4 toxicant (2000 mg/kg) Criteria used for interpretation of results: EU
Conclusions:
The acute dermal LD50 for undiluted Neodene 6 alpha olefin was reported to be >2000 mg/kg in rabbits.
Executive summary:

In an acute dermal toxicity study, groups of New Zealand White rabbits (4 male, 4 female) were dermally exposed to undiluted Neodene 6 at a dose of 2000 mg/kg bw. Each animal was treated at two application sites; one intact and one abraded. Controls (4 male, 4 female) were treated with deionised water. The treated skin was covered with surgical gauze and held in place with non-irritating adhesive tape, then covered with aluminium foil and an elastic bandage. The exposed area was gently washed after 24 hours of exposure and animals were observed at 1, 2, 4, 6, and 24 hours and twice daily for 14 days. Each exposure site was scored for degree of irritation according to the method of Draize following the removal of the occlusive covering until study termination. Body weights were determined on days -1, 0, 7, and 14. Survivors were necropsied on day 14.

All animals survived until end of study. There were no clinical signs of toxicity or effects on body weight. The skin was the only area affected with minimal irritation noted after the 24 -hour exposure period. By day 14, there was no evidence of irritation; however, at necropsy white crusty material on skin and fur, alopecia, and abrasions and focal reddened areas were noted in treated animals. Abrasions applied prior to treatment did not affect the results. The acute dermal LD50 for undiluted Neodene 6 alpha olefin was reported as >2000 mg/kg in rabbits.

This study received a Klimisch score of 1 and is classified as reliable without restriction because it was conducted in accordance with OECD 402 and was GLP compliant.

 

Data source

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

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Neodene 6
- Substance type: C6 alpha olefin
- Physical state: Liquid

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Ray Nichols Rabbitry, Lumberton, Texas
- Weight at study initiation: Weights recorded on day -1
- Fasting period before study: No
- Housing: Individually caged
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: 18 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.6 to 23.9
- Humidity (%): 36 to 71%
- Photoperiod (hrs dark / hrs light): 12 dark/12 light

IN-LIFE DATES: From: 1981-06-25 To: 1981-07-28

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: Not reported
- % coverage: Not reported
- Type of wrap if used: Surgical gauze secured with tape and covered with aluminium foil and an overwrap of an elastic Ace bandage

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Yes
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2.0 g/kg
- Constant volume or concentration used: No. Specific amount of test material administered was calculated using fasted body weights on day -1 and specific gravity of 0.673 for Neodene 6.
- Other: Each animal tested had two application sites (1 intact and 1 abraded)
Duration of exposure:
24 hours
Doses:
2000 mg/kg Neodene 6, 2 mL/kg deionised water (control)
No. of animals per sex per dose:
4
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations made at 1, 2, 4, and 6 hours following application, at 24 hours and twice daily thereafter until termination of study on day 14.
- Necropsy of survivors performed: Yes
- Other examinations performed: Clinical signs, body weight
Statistics:
Statistical analysis for significance of body weight changes included the calculation of the mean and standard error. Determination of the significance of body weight changes on days 7 and 14 compared to controls was made using an independent T-test. A probability level of 0.05 was used as criterion for significance. No information reported on method used to calculate LD50.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
No deaths were reported in this study.
Clinical signs:
No clinical signs of toxicity associated with administration of the test material were reported.
Body weight:
No significant reduction in body weight gain occurred in the test animals on either day 7 or day 14 as compared to the control group.
Gross pathology:
The only significant findings were related to the exposure sites and included white, crusty material on the skin and fur, alopecia, abrasions, and focal reddened areas.
Other findings:
Slight erythema and oedema were observed in all animals treated with Neodene 6 24 hours post-application. The average erythema and oedema scores for abraded skin animals were 0.8 and 1.4, respectively. The average erythema and oedema scores for intact skin animals were 0.5 and 1.2, respectively. All reported Draize scores were 0.0 on day 14 for all animals.

Any other information on results incl. tables

No tables included based on negative results.

Applicant's summary and conclusion

Interpretation of results:
other: Not classified
Remarks:
Not classified because LD50 is greater than the requirements for a Category 4 toxicant (2000 mg/kg) Criteria used for interpretation of results: EU
Conclusions:
The acute dermal LD50 for undiluted Neodene 6 alpha olefin was reported to be >2000 mg/kg in rabbits.
Executive summary:

In an acute dermal toxicity study, groups of New Zealand White rabbits (4 male, 4 female) were dermally exposed to undiluted Neodene 6 at a dose of 2000 mg/kg bw. Each animal was treated at two application sites; one intact and one abraded. Controls (4 male, 4 female) were treated with deionised water. The treated skin was covered with surgical gauze and held in place with non-irritating adhesive tape, then covered with aluminium foil and an elastic bandage. The exposed area was gently washed after 24 hours of exposure and animals were observed at 1, 2, 4, 6, and 24 hours and twice daily for 14 days. Each exposure site was scored for degree of irritation according to the method of Draize following the removal of the occlusive covering until study termination. Body weights were determined on days -1, 0, 7, and 14. Survivors were necropsied on day 14.

All animals survived until end of study. There were no clinical signs of toxicity or effects on body weight. The skin was the only area affected with minimal irritation noted after the 24 -hour exposure period. By day 14, there was no evidence of irritation; however, at necropsy white crusty material on skin and fur, alopecia, and abrasions and focal reddened areas were noted in treated animals. Abrasions applied prior to treatment did not affect the results. The acute dermal LD50 for undiluted Neodene 6 alpha olefin was reported as >2000 mg/kg in rabbits.

This study received a Klimisch score of 1 and is classified as reliable without restriction because it was conducted in accordance with OECD 402 and was GLP compliant.