Registration Dossier

Toxicological information

Repeated dose toxicity: dermal

Currently viewing:

Administrative data

Endpoint:
short-term repeated dose toxicity: dermal
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1977-05-04 to 1979-03-07
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
other: Significant methodological deficiencies

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1979
Report date:
1979

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 410 (Repeated Dose Dermal Toxicity: 21/28-Day Study)
Deviations:
yes
Remarks:
only one dose of 2mL/kg; 30 minutes exposure; reporting deficits
GLP compliance:
no
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Mercaptoacetic acid, monoester with propane-1,2,3-triol
EC Number:
250-264-8
EC Name:
Mercaptoacetic acid, monoester with propane-1,2,3-triol
Cas Number:
30618-84-9
Molecular formula:
C5H10O4S
IUPAC Name:
mercaptoacetic acid, monoester with propane-1,2,3-triol
Test material form:
solid - liquid: suspension
Details on test material:
- Name of test material (as cited in study report): Mixture of 22.3 parts of Glyceryl Mono Thioglycolate and 77.7 parts of Base Lotion #709-89-lC
- Analytical purity: no data

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Pel·Freez, Inc., USDA No. 7T-B-16, Rogers, Arkansas 72756
- Age at study initiation: 10 - 13 weeks
- Weight at study initiation: 2.38 - 2.84 kg
- Housing: Each animal was housed individually in a suspended, galvanized steel wire cage with dimensions of 14" x 16" x Z4"
- Diet: Ad libitum
- Water: Ad libitum
- Acclimation period: 12 days
- Fasting period before study: 24 h

ENVIRONMENTAL CONDITIONS: No data

Administration / exposure

Type of coverage:
open
Vehicle:
unchanged (no vehicle)
Details on exposure:
In preparation of the test, the sides of the back of each rabbit were clipped using electric clippers. A 3-square-inch patch of hair was left above the dorsal midline. The clipped area of each animal constituted approximately 10 percent of the total body surface area. The animals were then returned to their cages and 24 hours allowed to elapse, before the first mixture application was made. The waiting period permitted the skin to recover from the slight disturbance of the stratum corneum caused by the clipping procedure and also permit the healing of any microscopic abrasions possibly produced during the process. The clipping procedure was repeated at least once a week, but more often if necessary. To prevent oral ingestion of the test material, each animal was fitted with a lightweight, flexible plastic collar which was worn throughout the investigational period.

A mixture of 22.3 parts of - Glyceryl Mono Thioglycolate and 77.7 parts of Part Il Base Lotion #709-B9-1C was evaluated. The test material was applied to the unoccluded partially clipped, 3-square-inch test skin sites at a dose level of 2.0 mL/kg.

REMOVAL OF TEST SUBSTANCE
- Washing: Warm tap water
- Time after start of exposure: 30 minutes
Details on analytical verification of doses or concentrations:
Dose calculations were made weekly to adjust for changes in body weight.
Duration of treatment / exposure:
During the exposure period, the rabbits were placed in restrainers and subjected to a warm air flow from hair dryers installed above the rabbits. After
a 30 minute exposure period, the test sites were thoroughly rinsed with warm aerated tap water and then dried with towels and hair dryer.
Frequency of treatment:
These dosing procedures were followed 5 days per week for 4 weeks for a total of 20 applications.
Doses / concentrations
Remarks:
Doses / Concentrations:
2.0 mL/kg bw
Basis:
nominal per unit body weight
No. of animals per sex per dose:
5
Control animals:
yes, concurrent no treatment
Positive control:
not examined

Examinations

Observations and examinations performed and frequency:
Mortality: Daily

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Daily

DERMAL IRRITATION (if dermal study): Yes
- Time schedule for examinations: Daily

BODY WEIGHT: Yes
- Time schedule for examinations: days -12, -7, 14, 21, 28

FOOD CONSUMPTION:
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes / No / No data

FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: Yes / No / No data

WATER CONSUMPTION: No data

OPHTHALMOSCOPIC EXAMINATION: No

HAEMATOLOGY: Yes / No / No data
- Time schedule for collection of blood: Prior to start of study and after 28 days
- Anaesthetic used for blood collection: No
- Animals fasted: Yes, 24 h
- How many animals: All
- Parameters checked: Total Leukocyte Count, Erythrocyte Count, Hemoglobin Concentration, Hematocrit Value, Differential Leukocyte Count (Pucent and Absolute), Cell Indices (MCV. MCH and MCHC)


CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: Prior to start of study and after 28 days
- Anaesthetic used for blood collection: No
- Animals fasted: Yes, 24 h
- How many animals: All
- Parameters checked: Fasting Blood Glucose Concentration, Blood Urea Nitrogen Concentration (BUN), Serum Alkaline Phosphatase Activity (SAP), Serum Glutamic Pyruvic Transaminase Activity (SGPT), Serum Glutamic Oxalacetic Transaminase Activity (SGOT)


URINALYSIS: No

NEUROBEHAVIOURAL EXAMINATION: No
Sacrifice and pathology:
At the conclusion of the investigational period, all rabbits were sacrificed. This was followed by a gross pathologic examination.
Other examinations:
The weights of the brain, liver, kidneys, spleen, heart, gonads, thyroid glands and adrenal glands were recorded.
Statistics:
Kruskal Wallis test and multiple comparison tests

Results and discussion

Results of examinations

Clinical signs:
effects observed, treatment-related
Dermal irritation:
effects observed, treatment-related
Mortality:
mortality observed, treatment-related
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
not examined
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Haematological findings:
no effects observed
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
not examined
Behaviour (functional findings):
not examined
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
not specified
Histopathological findings: neoplastic:
not specified
Details on results:
Mortality: One rabbit died. Rabbit 5-M from the untreated control group died during the 7th test day. The animal exhibited diarrhoea on test days 3, 4 and 5 and died two days later over the weekend. The immediate cause of death was not evident from the pathologic studies but was attributed to naturally occurring disease.

Reactions: No treament related pharmacotoxic symptoms were noted. The test animals exhibited severe hair loss upon repeated dermal exposure to the test material.

Effects on Body Weights: No adverse body weight effects were observed.

Hematology Studies and Clinical Blood Chemistry: No treatment related hematologic effects were noted.

Effect levels

Dose descriptor:
NOAEL
Effect level:
2 other: mL/kg bw/day
Based on:
test mat.
Remarks:
22.3% GMT
Sex:
male/female

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

Table 1: Summary of Local Skin Reactions

Group

Local skin reactions after:

1 application

3 applications

5 applications

7 applications

untreated

No skin reactions

No skin reactions

No skin reactions

No skin reactions

treated with test substance

No skin reactions

No skin reactions

Noticeable hair 

loss 8/10

fissures 1/10

Noticeable hair 

loss 10/10

fissures 3/10

 

  

 Table 2: Continued summary of Local Skin Reactions 

 

Group

Local skin reactions after:

10 applications

12 applications

15 applications

20 applications

untreated

No skin reactions

No skin reactions

No skin reactions

No skin reactions

treated with test substance

Noticeable hair

 

loss 10/10

fissures 1/10

Noticeable hair loss 6/10, severe hair loss 3/10, complete hair loss 1/10

Noticeable hair loss 4/10, severe hair loss 5/10, complete hair loss 1/10

Noticeable hair loss 2/10, severe hair loss 6/10, complete hair loss 2/10

 

 

 

 

Applicant's summary and conclusion

Conclusions:
At 2 mL/kg Glycerol Monothioglycolate 22.3 % showed no treatment related mortality, pharmacotoxic reactions, effects on body weight or hematologic effects. Because no dose finding preleminary studies are available here, these findings can only be used as supporting study.