Registration Dossier

Administrative data

Endpoint:
epidemiological data
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Study period:
August 1993 to April 2006
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
It is a study that has been published in a peer reviewed journal. The restriction is also due to the use of the read across approach: the test was performed not with 3-PPB but with benzyl benzoate, a substance which has been demonstrated to be very similar in structure, physical/chemical properties and toxicological profile.

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
2007
Report Date:
2007

Materials and methods

Study type:
cohort study (retrospective)
Endpoint addressed:
developmental toxicity / teratogenicity
Test guideline
Qualifier:
no guideline required
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: as a lotion for topical application
Details on test material:
benzyl benzoate incorporated into a lotion for topical application for the treatment of scabies during pregnancy.

Method

Type of population:
other: Pregnant women, predominantly displaced people of Karen or Burmese origin in Tak Province, Thailand
Ethical approval:
not applicable
Details on study design:
HYPOTHESIS TESTED (if cohort or case control study): To assess the safety of benzoyl benzoate loation and permethrin, topical treatments for scabies during pregnancy. A retropective controlled cohort study.

METHOD OF DATA COLLECTION
- Type: Record review
- Details:

STUDY PERIOD: August 1993 to April 2006

SETTING: Antenatal clinics on the Thai-Burmese border.

STUDY POPULATION
- Total population (Total no. of persons in cohort from which the subjects were drawn): 29000
- Selection criteria: pregnant women treated with either Benzoyl benzoate or permethrin and with a known outcome (abortion or delivery)
- Total number of subjects participating in study:3200
- Sex/age/race: female
- Total number of subjects at end of study:
- Matching criteria: treated women matched 4 controls each
- Other:

COMPARISON POPULATION
- Type: Control or reference group from the same database who were not treated for scabies, based on smoking status, age (teenager <20 year old or adult), malaria during pregnancy, gravidity and period of inclusion into ante-natal clinics.
- Details:

HEALTH EFFECTS STUDIED
- Disease(s): Scabies
-

OTHER DESCRIPTIVE INFORMATION ABOUT STUDY:
Details on exposure:
Folowing clinical diagnosis of scabies treatment entailed a single full body application (excluding the face) of either benzyl benzoate lotion 25% (w/v) or permethrin 4%.

Results and discussion

Results:
Between August 1993 and April 2006, 711 pregnant women were treated or scabies with either Benzyl benzoate lotion (482) or permethrin (236); seen women were treated with both. After exclusion because of unknown delivery outcome the final anlaysis included 444 treated with benzoyl bezoate and 196 treated with permethrin. Six women were teated with both drugs and were therefore included in both groups for the analysis.
Most treatments were in the second (42.2%) or third trimesters (46.9%). The overall median of exposure was 24.5 weeks for BBL and 24.9 weeks for permethrin. For the 10.9% (n=66) of first trimester treatments the median gestation of exposure was 9.5 weeks.
444 women were treated with 559 benzoyl benzoate lotion applications (79.5%, 15.5%, 4.5% and 0.5% recieved 1,2,3 and 4 applications respectively. 196 women treated with permethrin and recieved 217 applications (90.3%, and 9.7% recieved one or two treatments respectively). Women were more likely to recieve a second treatment for scabies if the first treatment had been with benzoyl benzoate rather than permethrin.
The incidence of scabies peaked in January and August, being lowest in the warmer weather. There was a significant (P<0.001) correlation between the number of first treatments of scabies and the temperature, with a greater incidence of scabies during the coldest months.

Any other information on results incl. tables

Observational data demonstrating no increase in adverse pregnancy outcomes are important as they may be the only data to be critically evaluated.

The study suggests that benzoyl benzoate and permethrin are safe in the second and third trimesters of pregnancy.

Applicant's summary and conclusion

Conclusions:
There was no evidence of adverse effects on pregnancy outcome due to topical 25% BBL or 4% permethrin
Executive summary:

There were no statistically significant differences in pregnancy outcomes between women who were treated with either BBL (n = 444) compared with their matched controls (n = 1,776) or permethrin (n = 196) treated women and their matched controls (n = 784). Overall, only 10.9% (n = 66) of treatments were in the first trimester. Retreatment rates were higher with BBL 16.4%, than permethrin 9.7%, P = 0.038. Scabies was more common during cooler periods.

There was no evidence of adverse effects on pregnancy outcome due to topical 25% BBL or 4% permethrin