Prop-2-yn-1-ol

Repeated dose toxicity: dermal

Administrative data

Endpoint:

sub-chronic toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1965

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study performed prior to OECD Guidelines and GLP. However, study performance was similar to OECD Guideline 411 with acceptable restrictions.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1965

Report date:

1965

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 411 (Subchronic Dermal Toxicity: 90-Day Study)

Deviations:

not applicable

Principles of method if other than guideline:

The study was performed prior to existing OECD Guidelines, but can be regarded as equivalent or similar to OECD GL 411 with certain limitations.
- less than 20 animals were tested per dose group
- intact skin and abraded skin were exposed to test item
- no ophtamological examination was performed
- not all organs listed in OECD 411 were examined histopathologically

GLP compliance:

no

Remarks:

test predated GLP

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Prop-2-yn-1-ol

EC Number:

203-471-2

EC Name:

Prop-2-yn-1-ol

Cas Number:

107-19-7

Molecular formula:

C3H4O

IUPAC Name:

prop-2-yn-1-ol

Details on test material:

Test substance: Propargyl Alcohol 11-72063 - B.#155
Vehicle: distilled water

Test animals

Species:

rabbit

Strain:

other: albino rabbits

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: no information
- Age at study initiation: no information
- Weight at study initiation: 2 - 3 kg
- Fasting period before study: no information
- Housing: no information
- Diet (e.g. ad libitum): no information
- Water (e.g. ad libitum): no information
- Acclimation period: two weeks


ENVIRONMENTAL CONDITIONS
no information

Administration / exposure

Type of coverage:

open

Vehicle:

water

Details on exposure:

Route of Administration: dermal
Thirty-six albino rabbits in the weight range af 2-3 kg were set aside and observed for a period af two weeks to assure normality. The animals were then divided into four groups.
The test material was applled as w/v solutions in distiled water using 0%, 1. 0%, 0.3% and 0. 1% for controls, groups II , III and IV, respectively. Beginning on the 63rd day the daily dosage applied to group II was doubled, using a 2.0% solution. All dosages were applied In four equal increments, equally spaced through the day, five days per week. All animais were confined throughout each 8-hour exposure day. Control animals were handled in a manner similar to the test animais, applications of distilled water being made four times daily.

Analytical verification of doses or concentrations:

no

Duration of treatment / exposure:

13 weeks

Frequency of treatment:

5 days/week

Doses / concentrations

Remarks:

Doses / Concentrations:
1, 3 or 10 (20 beginning on day 63) mg/kg bw/day
Basis:
nominal per unit body weight

No. of animals per sex per dose:

4 - 5 rabbits/sex/dose and control group:
Group I (control): Males Intact skin 3, Abraded skin 2; Females Intact skin 2, Abraded skin 3; (n = 10),
Group II (10* mg/kg/day): Males Intact skin 3, Abraded skin 2; Females Intact skin 2, Abraded skin 3; (n = 10) (20* applied, starting on day 63),
Group III (3 mg/kg/day): Males Intact skin 2, Abraded skin 2; Females Intact skin 2, Abraded skin 2; (n = 8),
Group IV (1 mg/kg/day): Males Intact skin 2, Abraded skin 2; Females Intact skin 2, Abraded skin 2; (n = 8).

Control animals:

yes, concurrent vehicle

Details on study design:

All animals were weighed twice weekly during the first four weeks of the study and weekly thereafter, doses being adjusted. Hematology (hemoglobin, red blood cell count, white blood cell count, differential count) was performed prior to the experiment, at 45-days and at termination. Determination of alkaline phosphatase, blood urea nitrogen (BUN) and serum glutamlc pyruvic transaminase (SGPT) were performed prior to the start of the experiment, at 14-days and at 80-days. All rabbits were sacriflced for autopsy at terminatlon except for two rabblts (one control and one from Group II) sacrlficed at 28-days and two rabblts (one control and one from Group II) sacrificed at 56-days. Major organs of all animais were removed, weighed and tissues from the control and Group II animals were examined microscoplcally.

Positive control:

none

Examinations

Observations and examinations performed and frequency:

see "details on study design"

Sacrifice and pathology:

see "details on study design"

Statistics:

no data

Results and discussion

Results of examinations

Details on results:

CLINICAL SIGNS AND MORTALITY
No lethality occurred. No local effects were found. Other clinical signs were not reported.

BODY WEIGHT AND WEIGHT GAIN:
Analysis of the weight changes shows that there were no patterns of response attributable to the dosages applled. Neither the sex of the animals nor the condition of the skin at application (abraded or intact) appears to have any significant effect upon the experimental animals' weight changes as compared to those of the control animals.

FOOD CONSUMPTION: No information.

FOOD EFFICIENCY: No information.

WATER CONSUMPTION: No information.

OPHTHALMOSCOPIC EXAMINATION : Not performed.

HAEMATOLOGY:
Hematological findings in the experimental animais did not differ significantly from those of the control animais. All were within the normal limlts for the species.

CLINICAL CHEMISTRY (Blood chemistry):
Analysis of the values obtained for alkaline phosphatase, BUN (blood urea nitrogen), and SGPT (serum glutamic pyruvic transaminase) shows that there was no significant difference between any of the experimental groups as compared to the control group.

URINALYSIS: Not performed.

NEUROBEHAVIOUR: Not performed

ORGAN WEIGHTS / GROSS PATHOLOGY / HISTOPATHOLOGY::
No noteworthy observations were made upon gross examination of the animais at autopsy. Results of the microscopic examinatlon of the organs of the animals revealed no signiflcant differences between tissues from control and treated rabbits. All changes found were due to spontaneous disease or to the mechanical techniques of the study.

Effect levels

Dose descriptor:

NOAEL

Effect level:

> 10 - <= 20 mg/kg bw/day

Sex:

male/female

Remarks on result:

not determinable due to absence of adverse toxic effects

Remarks:

no systemic effects observed

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

Appllcation of Propargyl Alcohol 11-72063 - B. #155 to the intact or abraded skin of young adult rabblts in daily doses of up to 10 mg/kg over a 63-day period and up to 20 mg/kg over a 28-day perlod produced no systemic effects. At the dosages tested, Propargyl Alcohol 11-72063 - B.#155 does not constltute a systemic hazard by skin absorption in rabbits.

Applicant's summary and conclusion

Executive summary:

In a repeat-dose dermal toxicity study, Propargyl alcohol was applied as aqueous solution (0.1, 0.3 and 1-percent Propargyl alcohol in distilled water) to the intact and abraded skin of 2 - 3 male and female albino rabbits at dose levels of 0, 1, 3 and 10 mg/kg bw/day, 8 hours/day for 5 days/week during a 91-day period, beginning on day 63, the top dose was increased to 20 mg/kg bw/day.

Body weight gain changes and biochemical and hematological parameters did not differ significantly from those of the control group. No substance-related gross or microscopic tissue changes were observed. Application of Propargyl alcohol to the intact or abraded skin in daily doses of 1 or 3 mg/kg bw/day over a 90-day period, or 10 mg/kg bw/day for day 1-62 and subsequently 20 mg/kg bw/day for day 63-90 produced no systemic effects (including body weight gain, haematology, and histology). Furthermore, no local effects were seen.

The NOAEL derived from this study is 10 – 20 mg/kg bw/day.

This dermal toxicity study in the rabbit is acceptable and satisfies in general the guideline requirement for a repeat-dose dermal toxicity study (OECD GL 411) with some restrictions due to the fact that the study was performed prior to the existing guideline.