Study ID
Reference (title, number, year)	A Dietary Reproduction/Developmental Toxicity Screening Study in Rats, Study No. 1936‐012, 2020 (Documentation provided to EFSA No 3)
Source (published/unpublished)	Unpublished
Overview of the study and guideline
Good Laboratory Practice (yes/no)	Yes
Guideline study (if yes, specify)	OECD Guideline 421, adopted 29 July 2016
Animal model
Species and strain	CD® [Crl:CD®(SD)] rats
Disease models (e.g. diabetes, allergy, obesity)	None
Housing conditions
Housing condition	Individually housed, except during pairing, near parturition and during lactation
Diet name and source (if reported)	Meal Lab Diet ad libitum, tap water ad libitum
Treatment
Test material	Glycerol ester of wood rosin (GEWR) (from P. palustris and P. elliottii)
Provider	Pinova, Inc.
Compound purity	100%
Vehicle used	Diet
Dose regimen (dose level or concentration per group, and frequency) and achieved doses if available	0, 0.8, 1.8 and 3.4 w/w%. Beginning on GD 20, the females in Groups 2 to 4 were administered dietary concentrations at half the original concentrations (0, 0.4, 0.9 and 1.7%, respectively) to account for increased food consumption during the lactation period. Calculated doses for males: 0, 414, 976 and 1,842 mg/kg bw per day Calculated doses for females: 0, 504, 1,208 and 2,211 mg/kg bw per day (premating); 0, 520, 1,167 and 2,366 mg/kg bw per day (pregnancy); 0, 544, 1,237 and 2,446 mg/kg bw per day (lactation).
Route of administration (diet, drinking water, gavage)	Diet
Period of exposure (pre‐mating, mating, gestation, lactation, adult)	Female: from pre‐mating (14 days) to lactation (LD 13). Male: from pre‐mating (14 days) to euthanasia.
Duration of the exposure	50 days
Study design
Sex and age at the start of the treatment	12 males and 12 females per group (total 48 male and 48 female) age 9 weeks at least
Number animals/sex/group	12 males and 12 females for 4 groups
Measured endpoints	According to guideline
Time of measurement/observation period	According to guideline
Methods to measure the endpoints	According to guideline
Statistical analysis
Statistical methods	Group pair‐wise comparisons (ANOVA); Fisher's Exact Test with Stepdown Sidak Adjustment for few fertility indexes
Results
Findings reported by the study author/s	Nine of the 12 females in the high‐dose group (3.4%; equivalent to 1,842 mg/kg bw per day for males and 2,347 mg/kg bw per day for females) were pregnant. In one of these cases, the failure was likely due to the male, which was found to have small testes and epididymides at macroscopic evaluation and severe testicular atrophy at microscopic evaluation. In the other two cases, the reason(s) for the infertility remained unexplained. These findings were considered not to be treatment‐related by the authors.
No observed adverse effect level, lowest observed adverse effect level, benchmark dose/benchmark dose lower bound	Based on the absence of any test item‐related effects, the no‐observed‐effect‐level (NOEL) for reproductive and developmental toxicity, as well as general toxicity, was considered by the authors to be 3.4% (the highest concentration tested). This dietary concentration was equivalent to mean doses of 1,842 mg/kg bw per day for males and from 2,211 to 2,446 mg/kg bw per day for females.
Further information
Mis‐sexing of single pups was noted in two litters each of the control and the low‐dose group. This does not affect the validity of the study.
The Panel considered that due to lack of pregnancy in two females at the high dose, a more conservative NOAEL of 976 mg/kg bw per day (mid dose).

bw: body weight; CAS: Chemical Abstracts Service.