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Effects on fertility

Description of key information

No toxicity data on adverse effects on sexual function and fertility with barium 4-dodecylphenolate are available, thus the reproductive toxicity will be addressed with existing data on the individual moieties barium and dodecylphenolate.

Barium 4-dodecylphenolate is expected to impair fertility, since the moiety dodecylphenolate has shown adverse effects in a high quality 2-generation study. For the moiety barium, no classification is required based on the results of the prenatal developmental toxicity study.

Effect on fertility: via oral route
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEL
Study duration:
subchronic
Species:
rat
Quality of whole database:
high quality 2-generation study
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available
Additional information

Barium

Only two studies (NTP and Dietz) exist in which a dose-response relationship of different adverse effects on fertility after oral administration of barium chloride was investigated. These studies (see section 7.8.1) which were published in peer-reviewed journals were examined with respect to their adequacy for the derivation of NOAEL/LOAEL values for fertility impairment.

Based on these limited investigations with barium chloride as described above, a lack of fully, guideline conform data must be noted. Tentatively, the premating study by Dietz et al. (1992) on rats and mice may be considered as the only acceptable study for the derivation of a preliminary NOAEL for fertility effects of soluble barium compounds. This study investigated the occurrence of different adverse effects in male and female rats and mice and their offspring related to barium chloride exposure via drinking water. A tentative NOAEL for fertility impairment of 4,000 ppm in rats and 2,000 ppm in mice can be derived.

Screening study:

Fertility impairment in female rats: NOAEL of 179.5 mg Ba2+/kg bw/d; relates to 272 mg Barium chloride/kg bw/day (Dietz et al., 1992)

Fertility impairment in male rats: NOAEL of 201.5 mg Ba2+/kg bw/d; relates to 306 mg Barium chloride/kg bw/day (Dietz et al., 1992)

 

Only a screening test is available. However, based on this study there are no indications of a substantial impairment of fertility in rats up to the highest dose tested. Thus, the NOAEL was 4000 ppm (to average doses of 201.5 and 179.5 mg Ba/kg bw/d to male and female rats, respectively). No-observed-adverse-effect levels (NOAELs) on developmental toxicity for rats of 4000 ppm were derived. However, this NOAEL is of limited value to evaluate the potential for barium to induce developmental effects because there was no exposure of the females during gestation. For this reason, a testing proposal for a study investigating the effects on fertility was included into the registration dossier but a final decision has not yet been taken by ECHA.

Dodecylphenolate

 

In accordance with the SIDS Initial Assessment Profile (SIAP), “in rats, tetrapropenyl phenol causes a reduction in the fertility of both sexes and a reduction in mean live litter size, in the presence of general toxicity, at a dose of≥75 mg/kg/day. Effects on male and female reproductive organs were noted and some reduction in the growth rate of pups was observed during weaning at≤25 mg/kg/day. This substance causes adverse developmental effects in rats (skeletal variations and malformations and external variations) at 300 mg/kg/day, the highest dose tested, but only in the presence of maternal toxicity. Overall, the NOAEL for toxicity to reproduction is 5 mg/kg/day. At present there is no direct evidence of endocrine disruption. (SIAP, 2006)

 

References:

SIAP (2006): SIDS Initial Assessment Profile for Phenol, (tetrapropenyl) derivates; Tetrapropenyl phenol and Phenol, dodecyl-, branched; SIAM 22, 18-21 April 2006)

Barium 4-dodecylphenolate

Barium 4-dodecylphenolate is expected to show effects on fertility and development of the offspring, since the moiety dodecylphenolate has shown adverse effects in a high quality two-generation study.

For the moiety barium, no classification is required based on the results of the prenatal developmental toxicity study.

For the endpoint developmental toxicity, which is not a Reach Annex VIII (10-100 t/a) requirement, no robust study summaries were obtained. However, the license to use includes information that is included in the endpoint summary of IUCLID section 7.8 “Toxicity to reproduction”. Thus, a conclusion on developmental toxicity can be drawn based on the information stated therein.

Further testing is not required. For further information on the toxicity of the individual moieties, please refer to the relevant sections in the IUCLID and CSR.

 

Information on the individual moieties barium and dodecylphenolate will be used for the hazard assessment and, when applicable, for the risk characterisation of barium 4-dodecylphenolate. For the purpose of hazard assessment of barium 4-dodecylphenolate, the point of departure for the most sensitive endpoint of each moiety will be used for the DNEL derivation. For barium 4-dodecylphenolate, the NOAEL of 5 mg/kg bw/day for reproductive toxicity will be used

Effects on developmental toxicity

Description of key information

No toxicity data on adverse effects on sexual function and fertility with barium 4-dodecylphenolate are available, thus the reproductive toxicity will be addressed with existing data on the individual moieties barium and dodecylphenolate.

Barium 4-dodecylphenolate is expected to impair fertility, since the moiety dodecylphenolate has shown adverse effects in a high quality 2-generation study. For the moiety barium, no classification is required based on the results of the prenatal developmental toxicity study.

Effect on developmental toxicity: via oral route
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEL
Study duration:
subchronic
Species:
rat
Quality of whole database:
high quality 2-generation study
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no study available
Additional information

Barium

For the endpoint developmental toxicity, which is not a Reach Annex VIII (10-100 t/a) requirement, no robust study summaries were obtained. However, the license to use includes information that is included in the endpoint summary of IUCLID section 7.8 “Toxicity to reproduction”. Thus, a conclusion on developmental toxicity can be drawn based on the information stated therein (for detailed information please refer to the registration dossier of barium dichloride):

Developmental toxicity of barium chloride dihydrate was evaluated in a recent prenatal developmental toxicity study by daily administration of the test item at dose levels of 0, 10, 30 or 100 mg BaCl2 * 2 H2O/kg body weight to pregnant rats from gestation day 1 up to and including gestation day 20. No effects on body weights, food consumption and clinical signs were observed. Maternal toxicity was evidenced by the spontaneous deaths of two animals on gestation day 21 only and the conditional decline of another animal on gestation day 21 in the high dose group (100 mg BaCl2 * 2 H2O/kg bw).

No developmental toxicity or treatment-related observations, whatsoever in external, visceral and skeletal foetal examinations were observed in any dose level.

The NOAEL for maternal toxicity was therefore 30 mg/kg body weight barium chloride dihydrate (25.6 mg/kg bw barium chloride)). In absence of developmental effects, the NOAEL for prenatal developmental toxicity in the rat was ≥ 100 mg/kg body weight barium chloride dihydrate (≥85.3 mg/kg bw barium chloride).

Furthermore, tentative NOAEL values for developmental toxicity of 4,000 ppm and 2,000 ppm for rats and mice, respectively, are also reported in the study by Dietz et al. (1992). However, these NOAELs are of limited value to evaluate the potential for barium to induce developmental effects because the study design did not include prenatal exposure of the female animals to barium dichloride dihydrate. Therefore, this study has to be considered as inadequate for the assessment of the potential to induce developmental toxicity and cannot be used in a regulatory context.

Developmental toxicity: a NOAEL of >=85.3 mg BaCl2/kg was derived in an oral developmental toxicity study according to OECD 414.

No classification is required based on the results of the prenatal developmental toxicity study.

Dodecylphenolate

In accordance with the SIDS Initial Assessment Profile (SIAP), “the developmental toxicity study conducted by oral gavage indicates that tetrapropenyl phenol caused an increased incidence of skeletal and external malformations at a dose of 300 mg/kg/day, but only in the presence of marked maternal toxicity. In addition, there was a reduction in the growth rate of pups during weaning in the rat reproductive study at a dose level of 25 mg/kg/day, where parental toxicity was also observed. ” (SIAP, 2006)

 

 

References:

SIAP (2006): SIDS Initial Assessment Profile for Phenol, (tetrapropenyl) derivates; Tetrapropenyl phenol and Phenol, dodecyl-, branched; SIAM 22, 18-21 April 2006)

Barium 4-dodecylphenolate

Barium 4-dodecylphenolate is expected to show effects on fertility and development of the offspring, since the moiety dodecylphenolate has shown adverse effects in a high quality two-generation study.

For the moiety barium, no classification is required based on the results of the prenatal developmental toxicity study.

For the endpoint developmental toxicity, which is not a Reach Annex VIII (10-100 t/a) requirement, no robust study summaries were obtained. However, the license to use includes information that is included in the endpoint summary of IUCLID section 7.8 “Toxicity to reproduction”. Thus, a conclusion on developmental toxicity can be drawn based on the information stated therein.

Further testing is not required. For further information on the toxicity of the individual moieties, please refer to the relevant sections in the IUCLID and CSR.

 

Information on the individual moieties barium and dodecylphenolate will be used for the hazard assessment and, when applicable, for the risk characterisation of barium 4-dodecylphenolate. For the purpose of hazard assessment of barium 4-dodecylphenolate, the point of departure for the most sensitive endpoint of each moiety will be used for the DNEL derivation. For barium 4-dodecylphenolate, the NOAEL of 5 mg/kg bw/day for reproductive toxicity will be used

Justification for classification or non-classification

Barium 4-dodecylphenolateis expected to impair fertility, since the moiety dodecylphenolatehas shown adverse effects a high quality 2-generation study. For the moiety barium, no classification is required based on the results of the prenatal developmental toxicity study.

Thus, barium 4-dodecylphenolate is classified according to regulation (EC) 1272/2008 for reproductive toxicity in Category 1B (H360F).

This classification is in line with the harmonised classification of Phenol, dodecyl-, branched (Index No. 604-092-00-9)