11368209 and 11368213 represent the same study (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test). Information presented in both summaries is extracted together here under one study.

Reproductive Inhalation

Select Reproductive study type.

Extract the concentrations as 0, 50, 250, 580 ppm and also convert those to mg/m3. Be sure to copy and paste the information from the 'Details on analytical verification of doses or concentrations' into the Dosing description box. The high concentration was reduced from 1000 to 500 ppm beginning at exposure #7 on test day 9, so we are extracting the overall mean concentration (580 ppm) for that group, as reported in the ECHA summary. Exposure duration text should be entered as:

P0 females: up to 48d (14d premating-GD19; 6h/d, 5d/wk premating, 7d/wk mating/gestation)

P0 males: 36-37d (14d premating, 6h/d, 5d/wk; mating-sacrifice 7d/wk)

Create separate P0 male and P0 female groups and F1 male and female combined sex group. Use dummy variables for most endpoints (except organ weights, histopathology lesion incidence, and pup body weights) and set LOAELs based on statistically significant change from control (or based author's determination of test substance-related effect when no statistical analysis was done for an endpoint, or based on author's conclusion when a non-significant change was considered adverse). Copy results text describing the results for the specific endpoint you are extracting and paste it into results notes for each endpoint. If significance is stated, assume p-value of 0.05 (unless authors report a different p-value). For any endpoints reported in methods but not specifically discussed in results or executive summary, assume no treatment-related effects observed.

General toxicity endpoints reported in 11368209:

Clinical observation - group the clinical signs of toxicity together under EHV 5317 and indicate increase in high concentration male and female groups. Copy and paste results text into results notes.

Mortality - use dummy variables and indicate increase in high exposure male and female groups.

Terminal body weight and body weight gain 0-36d for males - indicate decreases in 250 and 580 ppm groups

Body weight at 14d and body weight gain 0-14d for females - indicate decrease in 580 ppm group

Feed consumption

Hematology all parameters mentioned in results

Clinical chemistry all parameters mentioned in results

Forelimb grip strength, hind limb grip strength, motor activity - no significant effects were observed. Results are described qualitatively in this ECHA record: https://echa.europa.eu/pt/registration-dossier/-/registered-dossier/5721/7/10/1. Copy and paste results text from that record into results notes for each endpoint that was evaluated and explain where the results are coming from.

Organ weights - extract means reported in results table on p. 9 (variances not reported)

Histopathology - extract incidence values for all lesions reported in results table on p. 10. These do not appear to be statistically analyzed and the underlining mentioned in the footnote does not show up in the table. Therefore, use the following descriptions from results text to set NOAEL/LOAEL:

Brain degeneration/necrosis - increased in 2 highest exposure groups
Lung, Alveolar histiocytosis - increased in males exposed to ≥250 ppm and in females exposed to highest concentration.
Spleen, Increased Extramedullary Hematopoiesis - increased in males exposed to ≥250 ppm and in females exposed to highest concentration.
Bone marrow, hyperplasia, erythrocytic - increased in in females exposed to highest concentration

Reproductive and Developmental endpoints reported in 11368213:

P0 Female endpoints:

mean number of pregnant animals

number of animals delivering

mating index

fertility index

precoital interval

gestation length

number of corpora lutea

number of implantation sites

percent of post implantation loss

number of litters born (litter size)

number of pups born alive (live litter size)

live born index

sex ratio

P0 Male endpoint:

Mating index

F1 male and female combined group endpoints:

Viability index (observation time PND0-4)

External malformations, total (observation time PND4)

Clinical observation (PND0-4) - no treatment-related effects

Pup body weight on PND0 and PND4 - extract quantitatively from results table on p. 7 of 11368213 ("Pup weight for the 250 and 1000/500 ppm groups was significantly lower compared to the control mean on postnatal day 4.")

ECHA, 2023, 11368209

Study evaluation

Animal bioassay experiments