TABLE F.3 Parameters examined in F1 generation animals. Only statistically significant changes are reported; ‘–’: no statistically significant changes were observed. Dose groups: G1: 0, G2: 16,000, G3: 20,000, G4: 25,000 mg/kg feed. Unless specified differently, the reported values for the respective parameters are within the historical control ranges.
| Parameters examined | F1 pups (surplus) | F1 pups (surplus) | F1 C1A | F1 C1A | F1 C1B | F1 C1B |
|---|---|---|---|---|---|---|
| Males | Females | Males | Females | Males | Females | |
| Mortality | – | – | – | – | – | – |
| Clinical signs | n.d. | n.d. | – | – | – | – |
| Behavioural examination during lactation | – | – | – | – | – | – |
| Detailed clinical examination | n.d. | n.d. | – | – | – | – |
| Mean body weight | PND21, ↓ G2 | PND21, ↓ G2 | PND21, 28, 35, 42: ↓ G2 | PND21, 28: ↓ G2 | PND 49, 56 to 112: ↑ G3 | PND 21 to 42: ↓ G2 |
| PND 95: ↑ G3 | ||||||
| Mean body weight gain | n.d. | n.d. | – | PND 21 to 42: ↑ G3 | PND 21–42 to 21–112: ↑ G3 | – |
| Feed consumption (during gestation) | n.a. | n.a. | n.a. | n.a. | n.a. | GD 1–7: ↑ G2 and G3 |
| GD 14–20: ↑ G2 | ||||||
| Haematology | n.d. | n.d. | – | Platelet count: ↑ G4 | n.d. | n.d. |
| Clinical biochemistry | n.d. | n.d. | – | – | n.d. | n.d. |
| Lymphocyte typing (spleen) | n.d. | n.d. |
T helper cells (CD4+): ↑ G2, G3 and G4, no dose‐related trend |
– | n.d. | n.d. |
| Urinalysis | n.d. | n.d. | – | – | n.d. | n.d. |
| Thyroid hormone levels |
TSH: PND 21, − |
TSH: PND 21, − |
TSH: – | TSH: ↑ G2 | n.d. | n.d. |
|
T4: PND4, ↑ G2; PND21, ↓ G4 |
T4: PND4, ↑ G2; PND21, ↓ G4 |
T4: – | T4: – | n.d. | n.d. | |
| Sexual maturation (body weight at balanopreputial separation) | n.d. | n.a. | ↓ G2 and G3 | n.a. | – | n.a. |
| Oestrous cycle data | n.a. | n.d. | n.a. | – | n.a. | – |
| Sperm parameters (mean daily sperm production) | n.d. | n.a. | ↓ G2 and G3 | n.a. | n.d. | n.a. |
| Necropsy and gross pathology | – | – | – | – | – | – |
| Histopathology | n.d | n.d. | – | – | n.d. | n.d. |
| Absolute organ weight |
PND 21: ↑ G3 spleen |
PND 21: ↓ G2 spleen; ↑ G3 spleen; ↓ G2 brain |
↓ G2 and G3 testes and iliac lymph nodes | ↑ G3, G4 thymus | ↑ G3 thymus | ↑ G4 thymus |
|
↓ G4 iliac lymph nodes |
↑ G4 spleen and iliac lymph nodes | ↑ G3 uterus with cervix | ||||
| Relative organ weight |
PND 21: ↑ G3 spleen |
PND 21: ↑ G3 spleen |
↓ G2, G3, G4 Iliac lymph nodes ↓ G3 testes, brain, liver ↑ G3 terminal bw |
– | ↓ G3 testes | ↑ G4 thymus |
| Reproductive parameters | n.d. | n.d. | n.d. | n.d. | – | – |
| Pre‐postnatal development | – | – | – | – | – | – |
| Pinna unfold and eye opening | ↓ G4 | ↓ G4 | ↓ G4 | ↓ G4 | ↓ G4 | ↓ G4 |
| Mean anogenital distance per litter | – | ↓ G4 | – | ↓ G4 | – | ↓ G4 |
| Anogenital distance ratio per litter | – | ↓ G3 and G4 | – | ↓ G3 and G4 | – | ↓ G3 and G4 |
| Sensory reflexes | – | – | – | – | – | – |
Abbreviations: ↑, increase; ↓, decrease; ‘–’, statistically not significant; G, dose group; GD, gestation day; PND, post‐natal day; n.a., not applicable; n.d., not determined.