Cumulated portion (% of individuals) of zebrafish (Danio rerio) embryos (n = 20–40) showing any lethal or sublethal effect after 120 h exposure to valproic acid and its nine analogues. The sequence of the chemicals represents the ranking in overall toxicity. Data in brackets: effective concentrations (µM), where 10% of the embryos show an effect (EC₁₀)

Concentration–response curves and EC₁₀ values for specific sublethal endpoints recorded after 120 h exposure of zebrafish (Danio rerio) embryos to various concentrations of valproic acid. Specific data given are EC₁₀ values (µM)

Pericardial edema (PE) and yolk edema (YE) as common effects recorded in zebrafish (Danio rerio) embryos after expsoure to VPA and all analogues (682 µM hexanoic acid; 96 hpf)

a Lordosis (2-methylhexanoic acid; 500 µM, 120 hpf) and b scoliosis (800 µM 2,2-dimethylvaleric acid; 120 hpf) as two of the most prominent observations after exposure of zebrafish (Danio rerio) embryos to VPA and its analogues

a Occurrence of the endpoint “small eyes” in zebrafish (Danio rerio) embryos exposed for 120 h to valproic acid and selected analogues. Data are given as % of affected embryos (n = 20–40). Due to the low occurrence of < 10% of effects at the highest test concentration and software limitations, the EC₁₀ values computed for 2-propylheptanoic acid, valproic acid, 2-ethylbutyric acid and 2-ethylhexanoic acid were greater than the highest concentration tested in the FETs. Whereas embryos exposed to 2-propylheptanoic acid, 4-ene valproic acid, 2,2-dimethylvaleric acid, valproic acid, 2-etyhlbutyric acid and 2-ethylhexanoic acid showed an increase in the number of individuals with decreased eye size, embryos exposed to 2-methylpentanoic acid, 2-methylhexanoic acid, 4-pentenoic acid and hexanoic acid did not show an effect. b (a) Normal development of eyes in 120 h old zebrafish (Danio rerio) embryos. (b) Endpoint "small eyes" in 120 h old zebrafish embryos after treatment with 100 µM 2-n-propylheptanoic acid. Area of interest outlined in red

Occurrence of the endpoint “jitter/tremor” in zebrafish (Danio rerio) embryos exposed for 120 h to valproic acid and selected analogues. Data are given as % of affected embryos (n = 20–40). Whereas embryos exposed to 2-n-propylheptanoic acid, valproic acid, 4-ene valproic acid, 2-ethylhexanoic acid, 2-methylhexanoic acid, 2,2-dimethylvaleric acid and hexanoic acid showed an increase in the number of individuals with tremor, embryos exposed to 2-methylpentanoic acid, 2-ethylbutyric acid and 4-pentenoic acid did not show an effect

a Occurrence of the endpoint “craniofacial deformation” in zebrafish (Danio rerio) embryos exposed for 120 h to valproic acid and selected analogues. Data are given as % of affected embryos (n = 20–40). Whereas embryos exposed to 2-n-propylheptanoic acid, valproic acid, 2-ethylhexanoic acid, 4-ene valproic acid, 2-methylpentanoic acid, 2,2-dimethylvaleric acid, hexanoic acid, 4-pentenoic acid and 2-methylhexanoic acid showed an increase in the number of individuals with craniofacial deformation, embryos exposed to 2-ethylbutyric acid did not show an effect. b (a) Normal development of craniofacial structures in 120 h old zebrafish (Danio rerio) embryos. (b) Endpoint “craniofacial deformation” in zebrafish embryos after treatment with 400 µM valproic acid: lower jaws are massively reduced in extension. Area of interest outlined in red