Registration Dossier

Administrative data

Endpoint:
sub-chronic toxicity: dermal
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
1993
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study well documented and in accordance to scientifically accepted principles, minor deviations to OECD guideline

Data source

Reference
Reference Type:
publication
Title:
Toxicology of diethylene glycol butyl ether 4. Dermal subchronic/reproduction study in rats.
Author:
Auletta CS, Schroeder RE, Krasavage WJ, Stack, CR
Year:
1993
Bibliographic source:
J. Am. Coll. Toxicol. 12(2), 161-168

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 411 (Subchronic Dermal Toxicity: 90-Day Study)
Deviations:
yes
Remarks:
minor deviations to OECD guideline
GLP compliance:
not specified
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: liquid
Details on test material:
- Name of test material (as cited in study report): diethylene glycol butyl ether (DGBE)
- Supplier: Dow Chemical Company
- Physical state: liquid
- Stability under test conditions: yes

Test animals

Species:
rat
Strain:
other: CD
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: CharlesRiver Lab., Raleigh,NC (USA)
- Age at study initiation: 8 weeks

- Housing: individually in suspended stainless steel cages
- Diet: Certified Purina Rodent Chow ad libitum
- Water: from Elizabethtown Water Company, ad libitum):
- Acclimation period: 2 weeks

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24
- Humidity (%): 30 - 70 %

- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Type of coverage:
occlusive
Vehicle:
water
Details on exposure:
TEST SITE
- Area of exposure: back
- % coverage: 3 x 3 cm area
- Type of wrap if used: polyethylene patch, covered by an adhesive banage wrapped around the trunk


REMOVAL OF TEST SUBSTANCE
- Washing (if done): residual test material was gently wiped from the application site
- Time after start of exposure: 6 hrs

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 200, 600 and 2000 mg/kg/d
- Concentration (if solution): undiluted, 30 % solution and 10 % solution
- Constant volume or concentration used: yes


Analytical verification of doses or concentrations:
yes
Duration of treatment / exposure:
13 weeks
Frequency of treatment:
5 days / week , 6 hrs daily
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 200, 600, 2000 mg/kg
Basis:
nominal per unit area
No. of animals per sex per dose:
10
Control animals:
yes
Details on study design:
- Post-exposure recovery period in satellite groups: no
Positive control:
no

Examinations

Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: twice daily

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule for examinations: each treatment day (5 days/week) prior to the application of the test article and after the wrappings were removed

DERMAL IRRITATION (if dermal study): Yes
- Time schedule for examinations: each treatment day (5 days/week) prior to the application of the test article and after the wrappings were removed

BODY WEIGHT: Yes
- Time schedule for examinations: weekly

FOOD CONSUMPTION: Yes
- Time schedule for examinations: weekly


OPHTHALMOSCOPIC EXAMINATION: Yes
- Time schedule for examinations: pre-study and near the end of the study

HAEMATOLOGY: Yes
- Time schedule for collection of blood: pre-study, after 1 month, and at the end of the study
- Anaesthetic used for blood collection: Yes (light)
- Animals fasted: Yes
- How many animals: all toxicity study animals


CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: pre-study, after 1 month, and at the end of the study
- Animals fasted: Yes
- How many animals: all toxicity study animals


URINALYSIS: Yes / No / No data
- Time schedule for collection of urine:
- Metabolism cages used for collection of urine: Yes / No / No data
- Animals fasted: Yes / No / No data
- Parameters checked in table [No.?] were examined.

NEUROBEHAVIOURAL EXAMINATION: Yes / No / No data
- Time schedule for examinations:
- Dose groups that were examined:
- Battery of functions tested: sensory activity / grip strength / motor activity / other:

OTHER:
Sacrifice and pathology:
GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes, incl. adrenal glands, kidneys, pituitary gland, prostate gland, testes, epididymides, seminal vesicles, liver, ovaries, spleen;
multiple sections of testes, epididymides and ovaries were prepared for examination
Other examinations:
During a 14-day period near the end of the study, daily vaginal smears were performed to determine whether normal estrous cycling was occurring.
Statistics:
Bartlett's test / ANOVA (parametric procedures)
Kruskal-Wallis test (non-parametric procedures)
Furtherly used: Dunn's summed-rank test; Jonckheere's test for monotonic trends for nonparametric comparisons; Fisher exact test.

Results and discussion

Results of examinations

Clinical signs:
effects observed, treatment-related
Description (incidence and severity):
see Urinalysis
Dermal irritation:
effects observed, treatment-related
Mortality:
mortality observed, treatment-related
Description (incidence):
see Urinalysis
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
no effects observed
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
no effects observed
Haematological findings:
no effects observed
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
effects observed, treatment-related
Description (incidence and severity):
slighlty increased incidence of occult urinary blood in mid-and high dose females
Behaviour (functional findings):
not specified
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
no effects observed
Details on results:
Female animals were significantly more sensitive to skin irritation

Effect levels

open allclose all
Dose descriptor:
LOAEL
Effect level:
200 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: Dermal irritation
Dose descriptor:
NOAEL
Effect level:
2 000 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: Systemic toxicity

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
No evidence for systemic toxicity in male and female rats; Skin irritation dependent on time, concentration and sex (pronounced effects in females).
Executive summary:

The alcohol Butyldigylycol (CAS 112-34-5) was tested for subchronic toxicity in a well conducted 90 d study in male and female rats (10 animals per sex and dose group). The substance was applied dermally at doses of 200, 600 and 2000 mg/kg. Dermal irritation occurred which was dependent on time and concentration. Female animals were significantly more sensitive. There was a slightly increased incidence of occult blood in the urine of 2 femals (mid-and high dose) which showed no clear time or dose dependency and was not confirmed by microscopic examination of the urine. There was no evidence for systemic toxicity by clinical and histopathological evaluations for all dose groups. Therefore, the NOAEL of the study can be determined to 2000 mg/kg/d.