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Toxicological information

Repeated dose toxicity: dermal

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Administrative data

Endpoint:
short-term repeated dose toxicity: dermal
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1982-08-05 to 1982-08-18
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: This study is classified as reliable with restrictions because even though it was conducted according to GLP standards, it did not conform to accepted harmonized guidelines, and only two exposure concentrations were used.
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:
short-term repeated dose toxicity: dermal
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Study period:
1982-08-05 to 1982-08-18
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: This study is classified as reliable with restrictions because even though it was conducted according to GLP standards, it did not conform to accepted harmonized guidelines, and only two exposure concentrations were used.
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:
no guideline available
Principles of method if other than guideline:
There are no guidelines for short-term studies with 9 days of exposure
GLP compliance:
yes
Species:
rat
Strain:
Fischer 344
Sex:
male/female
Vehicle:
other: Corn Oil
Duration of treatment / exposure:
6 hours
Remarks:
Doses / Concentrations:
1000 or 2000 mg/kg
Basis:

No. of animals per sex per dose:
5
Control animals:
yes
Critical effects observed:
not specified
Conclusions:
The repeated dermal application of Gulftene 12-16 resulted in histological changes in the skin at the site of application. These changes consisted of hyperplasia and thickening of the epidermis (acanthosis) and hyperkeratosis on the surface of the skin. In the test animals, these changes were often associated with acute dermatitis and focal ulceration of the epidermis.
Executive summary:

In a 9-day dermal toxicity study, Gulftene 12-16 was applied to the shaved skin of 5 Fischer 344 rats per sex per dose at dose levels of 0, 1000, or 2000 mg/kg bw/day, 6 hours per day on 9 non-consecutive days during a 2 week study period.

 

Body weight gains were reduced in the 2000 mg/kg group with the effect more notable in males. Severe dermal reactions occurred in the 2000 mg/kg group starting after the second treatment and continuing throughout the study period. They consisted of severe erythema (i.ebeet redness), slight to moderate eschar formation, very slight to slight edema, and slight to moderate desquamation. Slight to moderate hair loss occurred in nearly all animals after the 8th treatment and fissuring occurred in 4 of the 5 treated females after the 6thtreatment. Slight erythema occurred in 3 of the 10 animals exposed to 1000 mg/kg after 6 or 7 treatments, with one animal exhibiting a pinpoint spot of eschar. These changes were histopathologically confirmed. No effects were observed in hematology or clinical chemistry. There were several significant changes in organ weights in the 2000 mg/kg group that were related to the decreased body weights. Histopathology findings were only observed in the skin. NO NOAEL or LOAEL was reported in the study.

 

This study received a Klimisch score of 2 and is classified as reliable with restrictions because even though it was conducted according to GLP standards, it did not conform to accepted harmonized guidelines, and only two exposure concentrations were used.

This study was selected as a supporting study because it did not conform to accepted harmonized guidelines and only two expsoure contrations were evaluated; however, the study contains relevant and useful information, allowing it to qualify as a supporting study.

 

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1983
Report Date:
1983

Materials and methods

Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
There are no guidelines for short-term studies with 9 days of exposure
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Gulftene 12-16
- Substance type: C12-16 alpha olefins

Test animals

Species:
rat
Strain:
Fischer 344
Sex:
male/female

Administration / exposure

Vehicle:
other: Corn Oil
Duration of treatment / exposure:
6 hours
Doses / concentrations
Remarks:
Doses / Concentrations:
1000 or 2000 mg/kg
Basis:

No. of animals per sex per dose:
5
Control animals:
yes

Results and discussion

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
The repeated dermal application of Gulftene 12-16 resulted in histological changes in the skin at the site of application. These changes consisted of hyperplasia and thickening of the epidermis (acanthosis) and hyperkeratosis on the surface of the skin. In the test animals, these changes were often associated with acute dermatitis and focal ulceration of the epidermis.
Executive summary:

In a 9-day dermal toxicity study, Gulftene 12-16 was applied to the shaved skin of 5 Fischer 344 rats per sex per dose at dose levels of 0, 1000, or 2000 mg/kg bw/day, 6 hours per day on 9 non-consecutive days during a 2 week study period.

 

Body weight gains were reduced in the 2000 mg/kg group with the effect more notable in males. Severe dermal reactions occurred in the 2000 mg/kg group starting after the second treatment and continuing throughout the study period. They consisted of severe erythema (i.ebeet redness), slight to moderate eschar formation, very slight to slight edema, and slight to moderate desquamation. Slight to moderate hair loss occurred in nearly all animals after the 8th treatment and fissuring occurred in 4 of the 5 treated females after the 6thtreatment. Slight erythema occurred in 3 of the 10 animals exposed to 1000 mg/kg after 6 or 7 treatments, with one animal exhibiting a pinpoint spot of eschar. These changes were histopathologically confirmed. No effects were observed in hematology or clinical chemistry. There were several significant changes in organ weights in the 2000 mg/kg group that were related to the decreased body weights. Histopathology findings were only observed in the skin. NO NOAEL or LOAEL was reported in the study.

 

This study received a Klimisch score of 2 and is classified as reliable with restrictions because even though it was conducted according to GLP standards, it did not conform to accepted harmonized guidelines, and only two exposure concentrations were used.

This study was selected as a supporting study because it did not conform to accepted harmonized guidelines and only two expsoure contrations were evaluated; however, the study contains relevant and useful information, allowing it to qualify as a supporting study.