Buschmann J et al. 2013, 2555902 and ECHA , 2023, 11363018 are the same study. Endpoints reported in 11363018 that are not reported in 2555902 were added to this extraction with comments to indicate when results or methods were extracted from the ECHA summary (11363018).

(Full text link for HERO ID 11363018: https://echa.europa.eu/registration-dossier/-/registered-dossier/15086/7/9/2/?documentUUID=5de0b392-6a5b-4fda-a8cf-5fd155e9ae54)

P0 results to extract

Table 2 Mortality

Body weight gain, food consumption - qualitative statements, use dummy variables (may need multiple endpoints with different observation times to extract treatment-related findings at different timepoints)

Table 3 - all lesions (leave N blank (not zero) for dose groups not assessed)

Histopathology of other organs and tissues not in Table 3 - create an endpoint for each organ/tissue listed in methods and use dummy variables to indicate no treatment-related findings

From 11363018:

Clinical observation

Estrous cycle - for P0 females

Cauda epididymal sperm count, Percent motile sperm, Sperm morphology - for P0 males

Pre-coital interval - under both sexes

Number of successful matings (use EHV 16 Rats Mating) - under both sexes

Pregnancy rate - for P0 females

Absolute Organ weights (uterus, ovaries, testes, epididymides, seminal vessels, prostrate, liver, kidneys, adrenal glands, spleen, heart and lungs)

F1 Male and Female Sprague Dawley Pups (combined sex group)

From 11363018:

Offspring survival

F1 pup endpoints separated by sex:

Pup body weight, clinical observations - qualitative statements, use dummy variables

From 11363018:

It appears these were evaluated at weaning (PND21) in one male and one female of each litter:

Necropsy appeared normal

Pup body weight (terminal body weight)

Absolute Organ weights (heart, kidneys, liver and lungs)

"effects observed, treatment-related: In the high dose group, all organ weights were decreased compared to the control group. This reached statistical significance in males for heart and lung, and in females for ovaries, kidneys, liver, heart and lungs. This also occurred in the heart of females of the medium dose group. This decrease could be a result of the lower terminal body weight of the pups in the high dose group."

Histopathology (heart, kidneys, liver and lungs)

"effects observed, non-treatment-related: Findings in the heart and kidney were equally divided in the control and high level groups. There were no other reported findings."

P1 Male Spraque Dawley Rats and P1 Female Sprague Dawley Rats:

Mortality during lactation - quantitative data in text

Maternal body weight, body weight gain, and food consumption during gestation and lactation, - qualitative statements, use dummy variables

Pre-coital time - qualitative statement, use dummy variables

No. of pregnancies, Dams with liveborn pups - quantitative data in text

Table 4 - all lesions (leave N blank (not zero) for dose groups not assessed)

Histopathology of other organs and tissues not in Table 4 - create an endpoint for each organ/tissue listed in methods and use dummy variables to indicate no treatment-related findings (check to be sure all mentioned in ECHA summary are included: vagina, uterus, oviducts, cervix, ovaries, testes one epididymis, seminal vessels, prostate, coagulating glands, brain, heart kidneys, liver, lungs).

Ovarian follicle count - quantitative data in text

Serum LDH, CK, AST activity - qualitative statements, use dummy variables

From 11363018:

"Sexual maturation was comparable across all groups" - extract as vaginal opening for females and preputial separation for males

"locomotor activity using the ActiMot/Motitest computerised light beam system. Between day 30 and 60 learning and memory was tested using an M water maze." "Evaluations of locomotor activity, learning and memory were unaffected. "

Absolute Organ weights (uterus, ovaries, testes, epididymides, seminal vessels, prostrate, liver, kidneys, adrenal glands, spleen, heart and lungs)

Cauda epididymal sperm count, Percent motile sperm, Sperm morphology - for P1 males ("there were no treatment related findings on examination of sperm")

F2 Male and Female Sprague Dawley Pups (combined sex group):

From 11363018:

Number of stillborn pups

Litter size

Pups not surviving to PND4

F2 pup endpoints separated by sex

From 11363018:

Clinical observations

Necropsy appeared normal

Absolute Organ weights (heart, kidneys, liver, lungs, and brain)

Histopathology (heart, kidneys, liver and lungs)

"Dilated tubules and interstitial fibrosis" - extract as 1 kidney histopathology endpoint for females only

F2 Male and Female Sprague Dawley Rat Pups