Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
toxicity to reproduction: other studies
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1986
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
The methods followed were comprehensively documented in the report. The report included GLP and Quality Assurance statements, signed by the Study Director and Head of the QA Unit, respectively. Although not specifically referenced in the report, generally the study followed EPA Protocol Guideline 870.3200 "21/28-Day dermal toxicity" and OECD 410: "Repeated Dose Dermal Toxicity: 21/28 day." Specifically, the numbers and type of test animals used and their husbandry conditions followed guidance. Test material characterization was adequate. The amount of test material applied complied with guidance, the length of the treatment period was sufficient for this type of test, and evaluation criteria and statistical methods were typical for this type assay and adequately recorded.
Cross-referenceopen allclose all
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1986
Report date:
1986

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
other: Guideline 870.3200 "21/28-Day dermal toxicity" and OECD 410: "Repeated Dose Dermal Toxicity: 21/28 day."
Principles of method if other than guideline:
not applicable
GLP compliance:
yes
Type of method:
in vivo

Test material

Constituent 1
Chemical structure
Reference substance name:
1-phenoxypropan-2-ol
EC Number:
212-222-7
EC Name:
1-phenoxypropan-2-ol
Cas Number:
770-35-4
Molecular formula:
C9H12O2
IUPAC Name:
1-phenoxypropan-2-ol
Constituent 2
Reference substance name:
1-phenylpropan-2-ol
EC Number:
211-821-0
EC Name:
1-phenylpropan-2-ol
Cas Number:
698-87-3
IUPAC Name:
1-phenylpropan-2-ol
Details on test material:
Identity: Dowanol-PPh (1-phenoxy-2-hydroxypropane or propylene glycol phenyl ether). CAS # 770-35-4 (also 41593-38-8)
Batch No.: LE08011T01
Purity: 95.55% (4.37% DiPPh, 0.08% Phenol)
Supplied as: Not reported
Vapor Pressure: <1.0 mmHg
Specific Gravity: 1.059
Appearance: Liquid

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Age at dosing: Approximately 5 months of age
- Source: Hazleton-Dutchland, Inc., Denver, PA
- Acclimation period: At least 14 days
- Average weight at start of study: 3-4 kilograms
- Assignment to groups: Computer generated, random number tables
- Diet: Certified Rabbit Chow #5322 (Ralston Purina Company, St. Louis, MO)
- Access to food: Restricted to 8 ounces per day
- Access to water: Available ad libitum in glass bottles
- Method of Identification: Ear tags
- Housing: Individually in stainless steel cages with wire-mesh bottoms

ENVIRONMENTAL CONDITIONS (for non-exposure periods):
- Temperature: ~20°C (Recording frequency not reported)
- Humidity: ~50%. (Recording frequency not reported)
- Air changes: Not specified
- Photoperiod: 12 hr light/12 hr dark

Administration / exposure

Route of administration:
dermal
Type of inhalation exposure (if applicable):
other: not applicable
Vehicle:
unchanged (no vehicle)
Details on exposure:
Propylene glycol phenyl ether was applied daily to the clipped dorsal skin of rabbits (5/sex/dose) at doses of 0, 100, 300, or 1000 mg/kg body weight/day, 5 days/week, over a period of 4 weeks (total of 19 applications). The control group was treated with approximately 1 ml/kg/day distilled water. Propylene glycol phenyl ether was applied uniformly over a 10 x 15 cm area of the back using a syringe with a blunt needle. The dose was covered with gauze, non-absorbent cotton, then an occlusive bandage, all held in place for 6 hours with a lycra/spandex jacket. After the 6 hour exposure period, the bandage was removed and the area washed clean of Propylene glycol phenyl ether with a water-dampened towel.
Analytical verification of doses or concentrations:
no
Details on analytical verification of doses or concentrations:
not applicable
Duration of treatment / exposure:
28 days
Frequency of treatment:
Once daily, 5 days/week (19 applications total)
Duration of test:
28 days
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
100 mg/kg body weight/day
Basis:
nominal conc.
Remarks:
Doses / Concentrations:
300 mg/kg body weight/day
Basis:
nominal conc.
Remarks:
Doses / Concentrations:
1000 mg/kg body weight/day
Basis:
nominal conc.
No. of animals per sex per dose:
5 rabbits/sex/dose
Control animals:
other: yes, distilled water (~1 ml/kg)
Details on study design:
Propylene glycol phenyl ether was applied daily to the clipped dorsal skin of rabbits (5/sex/dose) at doses of 0, 100, 300, or 1000 mg/kg body weight/day, 5 days/week, over a period of 4 weeks (total of 19 applications). The control group was treated with approximately 1 ml/kg/day distilled water. Propylene glycol phenyl ether was applied uniformly over a 10 x 15 cm area of the back using a syringe with a blunt needle. The dose was covered with gauze, non-absorbent cotton, then an occlusive bandage, all held in place for 6 hours with a lycra/spandex jacket. After the 6 hour exposure period, the bandage was removed and the area washed clean of Propylene glycol phenyl ether with a water-dampened towel.
Over the course of the study, rabbits were monitored for clinical signs of toxicity, body weight changes, hematological, clinical chemistry, and urinalysis changes, as well as gross and microscopic pathology.
Reproductive organs were weighed and subjected to gross and histopathological evaluation. Testis of the males were weighted but female reproductive organs were not. In control and high dose males, the following reproductive tissues were examined microscopically: testis, epididymides, seminal vesicles, and prostate. In control and high dose females, the following reproductive tissues were examined: mammary glands, ovaries, oviducts, uterus, cervix, and vagina
Statistics:
Descriptive statistics (mean and standard deviation) were reported for white blood cell differential counts and red blood cell indices. Body weights, absolute and relative organ weights, clinical chemistry data and hematology data were evaluated by Bartlett's test for equality of variances. Based on the outcome of Bartlett's test, exploratory data analyses were performed by a parametric or non-parametric analysis of variance (ANOVA), followed respectively by Dunnett's test or the Wilcoxon Ran-Sum test with a Bonferroni correction for multiple comparisons. Statistical outliers were identified by a sequential test and excluded accordingly

Results and discussion

Effect levels

Dose descriptor:
NOAEL
Effect level:
1 000 mg/kg bw/day
Sex:
male/female
Basis for effect level:
other: No toxicity to reproductive organs was evident based on organ weights, gross observation, or microscopic examination

Observed effects

All rabbits survived treatment with no changes in body weights and no overt signs of systemic toxicity. All subjects showed some dermal irritation at the site of Propylene glycol phenyl ether application, characterized by moderate exfoliation and hyperemia in the high dose group, slight exfoliation and transient hyperemia in the mid-dose group, and very slight exfoliation in the low dose group. No changes were noted in absolute or relative organ weights compared to controls. No consistent changes were noted in clinical laboratory studies other than a slight increase in platelet counts in males, which was statistically significant in high dose group and approached significance in mid-dose males. Females showed no platelet response to Propylene glycol phenyl ether exposure. No histopathological changes were noted upon examination of tissues from the high-dose subjects.
Reproductive Organs: No significant differences in testes weights were evident among Propylene glycol phenyl ether treated males. Female reproductive organs were not weighed. In males, gross examination revealed no unusual lesions of testes, epididymides, seminal vesicles, or prostate. In females, gross examination revealed no abnormalities of mammary glands, ovaries, oviducts, uterus, cervix, or vigina. The testis of control and high dose
males were normal. Epididymides of all of the high dose males were normal but one of the controls had very slight chronic interstitial unilateral inflammation and a second control had slight granulomatous, unilateral inflammation of the musculature. Seminal vesicles of all control and treated males were normal. The prostates of all control and treated males were normal. In females, ovaries, oviducts, uteri, cervix, and vagina all were normal. Mammary glands of two of the control females exhibited galactocels but all Propylene glycol phenyl ether treated females were normal. To summarize, no reproductive toxicity was evident from treatment with Propylene glycol phenyl ether.

Any other information on results incl. tables

none

Applicant's summary and conclusion

Conclusions:
Propylene glycol phenyl ether applied dermally to the backs of rabbits for 6 hr/day, 5 days/wk over a 28 day period produced no toxicity at dose levels up to 1000 mg/kg-day. This study established a NOAEL of 1000 mg/kg-day. No toxicity to reproductive organs was evident based on organ weights, gross observation, or microscopic examination.
Executive summary:

Propylene glycol phenyl ether was applied dermally at levels of 100, 300 and 1000 mg/kg body weight/day to the backs of rabbits (5 rabbits/sex/dose) for 6 hr/day, 5 days/wk over a 28 day period (total of 19 applications). The control group was treated with approximately 1 ml/kg/day distilled water. Propylene glycol phenyl ether was applied uniformly over a 10 x 15 cm area of the back using a syringe with a blunt needle. The dose was covered with gauze, non-absorbent cotton, then an occlusive bandage, all held in place for 6 hours with a lycra/spandex jacket. After the 6 hour exposure period, the bandage was removed and the area washed clean of Propylene glycol phenyl ether with a water-dampened towel.

All rabbits survived treatment with no changes in body weights and no overt signs of systemic toxicity. All subjects showed some dermal irritation at the site of Propylene glycol phenyl ether application, characterized by moderate exfoliation and hyperemia in the high dose group, slight exfoliation and transient hyperemia in the mid-dose group, and very slight exfoliation in the low dose group. No changes were noted in absolute or relative organ weights compared to controls. No consistent changes were noted in clinical laboratory studies other than a slight increase in platelet counts in males, which was statistically significant in high dose group and approached significance in mid-dose males. Females showed no platelet response to Propylene glycol phenyl ether exposure. No histopathological changes were noted upon examination of tissues from the high-dose subjects.

Reproductive Organs: No significant differences in testes weights were evident among Propylene glycol phenyl ether treated males. Female reproductive organs were not weighed. In males, gross examination revealed no unusual lesions of testes, epididymides, seminal vesicles, or prostate. In females, gross examination revealed no abnormalities of mammary glands, ovaries, oviducts, uterus, cervix, or vigina. The testis of control and high dose males were normal. Epididymides of all of the high dose males were normal but one of the controls had very slight chronic interstitial unilateral inflammation and a second control had slight granulomatous, unilateral inflammation of the musculature. Seminal vesicles of all control and treated males were normal. The prostates of all control and treated males were normal. In females, ovaries, oviducts, uteri, cervix, and vagina all were normal. Mammary glands of two of the control females exhibited galactocels but all Propylene glycol phenyl ether treated females were normal. To summarize, no reproductive toxicity was evident from treatment with Propylene glycol phenyl ether.

This study established a NOAEL of 1000 mg/kg-day. No toxicity to reproductive organs was evident based on organ weights, gross observation, or microscopic examination.