Registration Dossier

Reference

Endpoint:

one-generation reproductive toxicity

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Justification for type of information:

Relevant information for the 2 degradation products: Hydrogen chloride:
No reliable studies have been reported regarding toxicity to reproduction and development in animals after oral, dermal or inhalation exposure to hydrogen chloride/hydrochloric acid. Because protons and chloride ions are normal constituents in the body fluid of animal species, low concentrations of hydrogen chloride gas/mist or solution do not seem to cause adverse effects to animals. In fact, the cells of gastric glands secrete hydrochloric acid into the cavity of the stomach and orally administered sulfuric acid, which results in pH change as well, did not cause developmental toxicity to laboratory animals. These facts indicate that hydrogen chloride/hydrochloric acid is not expected to have developmental toxicity. In addition, no effects on the gonads were observed in a good quality 90-day inhalation study up to 50 ppm.
The local effects of HCl are predominant for repeated dose toxicity (including reproduction toxicity) compared to systemic effects, which as e.g. reduced body weight in 90-days toxicity studies are probably a sequel of the local effects. As reported under Section 7.5 a NOAEC of 15 mg HCl/m³, 6 h/d, 5 d/week, was derived from 90-day and 2-years inhalation toxicity studies. The NOAEC of 15 mg HCl/m³ corresponds to 16 mg BCl3/m³ or to a NOAEL of 6.1 mg BCl3/kg bw/d.

Boric acid:
The second degradation product, after BCl3 is coming into contact with water, i.e. boric acid, is classified under CLP as Repr. 1B, H360 FD. 'F' for fertility and 'D' for developmental toxicity. A classification as Repr. 1B, H360 FD is required for mixtures of boric acid at concentrations of ≥5.5 % which is remarkably higher for boric acid than the general concentration limit of 0.3 % v/v, set in Table 3.7.2 of Annex I of CLP. By setting this higher limit concentration it is expressed that the toxic effects of boric acid have a defined threshold and that the toxic effects are of lower concern, compared to other substances classified as Repr. 1B, H360 FD.
A series of studies, also on humans, are reported in the IUCLID for boric acid. An overall lowest NOAEL of 100 mg/kg bw/d is presented for fertility impairment, detected in a multigeneration study in rats.
NOAELfertiliy = 100 mg B(OH)3/kg bw/d corresponds to 192 mg BCl3/kg bw/d. Converting the NOAELoral = 192 mg/kg bw to the more relevant inhalation exposure a NOAECinhal,8h/d = (192 mg/kg)/(0.38 m³/kg/d) * (6.7 m³/10 m³) * (100 %/100 %) = 340 mg BCl3/m³ is obtained. The conversion to a NOAEC was performed according to the ECHA Guidance on Info and CSA R.8 Figure R.8-3, assuming a workers exposure of 8 h/d and a 100 % absorption for inhalation and oral dosing and for rats and human. The 100 % absorptions are justified, see Section 7.1 on Toxicokinetics.

Endpoint conclusion:
It is concluded that the local toxic effects of HCl occur at concentrations of >16 mg BCl3/m³ whereas boric acid causes reproductive effects only at 21 times higher doses of 340 mg/m³. Reproductive effects therefore could only occur at doses already causing significant local toxic effects or in other words at maternal and paternal toxic doses. It is quite certain that anyone exposed to concentrations remarkable higher than 16 mg BCl3/m³ will react to the burning/itching skin and respiratory sensation and will automatically start to wear PPE. If risk management measures are applied to prevent toxic effects by HCl then also the reproduction toxic effects of boric acid would be prevented.
The NOAECfertiliy = 340 mg BCl3/m³.

Principles of method if other than guideline:

A category approach is applied.

Dose descriptor:

NOAEL

Effect level:

100 mg/kg bw/day (nominal)

Based on:

other: boric acid.

Sex:

male/female

Basis for effect level:

other: see 'Remark'

Remarks on result:

other: Generation: P + F1 + F2 (migrated information)

Dose descriptor:

NOAEL

Effect level:

192 mg/kg bw/day

Based on:

other: BCl3, transcribed from the NOAEL = 100 mg/kg for boric acid.

Sex:

male/female

Remarks on result:

other: Generation: P + F1 + F2 (migrated information)

Dose descriptor:

NOAEC

Effect level:

340 mg/m³ air

Based on:

other: BCl3.

Sex:

male/female

Basis for effect level:

other: see 'Remark'

Remarks on result:

other: Generation: P +F1 +F2 (migrated information)

Reproductive effects observed:

not specified

Relevant information for the 2 degradation products: Hydrogen chloride:

No reliable studies have been reported regarding toxicity to reproduction and development in animals after oral, dermal or inhalation exposure to hydrogen chloride/hydrochloric acid. Because protons and chloride ions are normal constituents in the body fluid of animal species, low concentrations of hydrogen chloride gas/mist or solution do not seem to cause adverse effects to animals. In fact, the cells of gastric glands secrete hydrochloric acid into the cavity of the stomach and orally administered sulfuric acid, which results in pH change as well, did not cause developmental toxicity to laboratory animals. These facts indicate that hydrogen chloride/hydrochloric acid is not expected to have developmental toxicity. In addition, no effects on the gonads were observed in a good quality 90-day inhalation study up to 50 ppm.

The local effects of HCl are predominant for repeated dose toxicity (including reproduction toxicity) compared to systemic effects, which as e.g. reduced body weight in 90-days toxicity studies are probably a sequel of the local effects. As reported under Section 7.5 a NOAEC of 15 mg HCl/m³, 6 h/d, 5 d/week, was derived from 90-day and 2-years inhalation toxicity studies. The NOAEC of 15 mg HCl/m³ corresponds to 16 mg BCl3/m³ or to a NOAEL of 6.1 mg BCl3/kg bw/d.

Boric acid:

The second degradation product, after BCl3 is coming into contact with water, i.e. boric acid, is classified under CLP as Repr. 1B, H360 FD. 'F' for fertility and 'D' for developmental toxicity. A classification as Repr. 1B, H360 FD is required for mixtures of boric acid at concentrations of ≥5.5 % which is remarkably higher for boric acid than the general concentration limit of 0.3 % v/v, set in Table 3.7.2 of Annex I of CLP. By setting this higher limit concentration it is expressed that the toxic effects of boric acid have a defined threshold and that the toxic effects are of lower concern, compared to other substances classified as Repr. 1B, H360 FD.

A series of studies, also on humans, are reported in the IUCLID for boric acid. An overall lowest NOAEL of 100 mg/kg bw/d is presented for fertility impairment, detected in a multigeneration study in rats.

NOAELfertiliy = 100 mg B(OH)3/kg bw/d corresponds to 192 mg BCl3/kg bw/d. Converting the NOAELoral = 192 mg/kg bw to the more relevant inhalation exposure a NOAECinhal,8h/d = (192 mg/kg)/(0.38 m³/kg/d) * (6.7 m³/10 m³) * (100 %/100 %) = 340 mg BCl3/m³ is obtained. The conversion to a NOAEC was performed according to the ECHA Guidance on Info and CSA R.8 Figure R.8-3, assuming a workers exposure of 8 h/d and a 100 % absorption for inhalation and oral dosing and for rats and human. The 100 % absorptions are justified, see Section 7.1 on Toxicokinetics.

Endpoint conclusion:

It is concluded that the local toxic effects of HCl occur at concentrations of >16 mg BCl3/m³ whereas boric acid causes reproductive effects only at 21 times higher doses of 340 mg/m³. Reproductive effects therefore could only occur at doses already causing significant local toxic effects or in other words at maternal and paternal toxic doses. It is quite certain that anyone exposed to concentrations remarkable higher than 16 mg BCl3/m³ will react to the burning/itching skin and respiratory sensation and will automatically start to wear PPE. If risk management measures are applied to prevent toxic effects by HCl then also the reproduction toxic effects of boric acid would be prevented.

The NOAECfertiliy = 340 mg BCl3/m³.

Conclusions:

It is concluded that the local toxic effects of HCl occur at concentrations of >16 mg BCl3/m³ whereas the other degradation product of BCl3, i.e. boric acid, causes reproductive effects only at 21 times higher doses:
The NOAECfertiliy = 340 mg BCl3/m³.

Executive summary:

A degradation category approach is applied, based on the very rapid and complete degradation (hydrolysis) of boron trichloride in water to form hydrochloric acid and boric acid. The description and justification of the category is presented in Section 13. The endpoint results of the degradation products are transcribed to boron trichloride.

Hydrogen chloride:

No reliable studies have been reported regarding toxicity to reproduction and development in animals after oral, dermal or inhalation exposure to hydrogen chloride/hydrochloric acid. Because protons and chloride ions are normal constituents in the body fluid of animal species, low concentrations of hydrogen chloride gas/mist or solution do not seem to cause adverse effects to animals. In fact, the cells of gastric glands secrete hydrochloric acid into the cavity of the stomach and orally administered sulfuric acid, which results in pH change as well, did not cause developmental toxicity to laboratory animals. These facts indicate that hydrogen chloride/hydrochloric acid is not expected to have developmental toxicity. In addition, no effects on the gonads were observed in a good quality 90-day inhalation study up to 50 ppm.

The local effects of HCl are predominant for repeated dose toxicity (including reproduction toxicity) compared to systemic effects, which as e.g. reduced body weight in 90-days toxicity studies are probably a sequel of the local effects. As reported under Section 7.5 a NOAEC of 15 mg HCl/m³, 6 h/d, 5 d/week, was derived from 90-day and 2-years inhalation toxicity studies. The NOAEC of 15 mg HCl/m³ corresponds to 16 mg BCl3/m³ or to a NOAEL of 6.1 mg BCl3/kg bw/d.

Boric acid:

The second degradation product, after BCl3 is coming into contact with water, i.e. boric acid, is classified under CLP as Repr. 1B, H360 FD. 'F' for fertility and 'D' for developmental toxicity. A classification as Repr. 1B, H360 FD is required for mixtures of boric acid at concentrations of ≥5.5 % which is remarkably higher for boric acid than the general concentration limit of 0.3 % v/v, set in Table 3.7.2 of Annex I of CLP. By setting this higher limit concentration it is expressed that the toxic effects of boric acid have a defined threshold and that the toxic effects are of lower concern, compared to other substances classified as Repr. 1B, H360 FD.

A series of studies, also on humans, are reported in the IUCLID for boric acid. An overall lowest NOAEL of 100 mg/kg bw/d is presented for fertility impairment, detected in a multigeneration study in rats.

NOAELfertiliy = 100 mg B(OH)3/kg bw/d corresponds to 192 mg BCl3/kg bw/d. Converting the NOAELoral = 192 mg/kg bw to the more relevant inhalation exposure a NOAECinhal,8h/d = (192 mg/kg)/(0.38 m³/kg/d) * (6.7 m³/10 m³) * (100 %/100 %) = 340 mg BCl3/m³ is obtained. The conversion to a NOAEC was performed according to the ECHA Guidance on Info and CSA R.8 Figure R.8-3, assuming a workers exposure of 8 h/d and a 100 % absorption for inhalation and oral dosing and for rats and human. The 100 % absorptions are justified, see Section 7.1 on Toxicokinetics.

Endpoint conclusion:

It is concluded that the local toxic effects of HCl occur at concentrations of >16 mg BCl3/m³ whereas boric acid causes reproductive effects only at 21 times higher doses of 340 mg/m³. Reproductive effects therefore could only occur at doses already causing significant local toxic effects or in other words at maternal and paternal toxic doses. It is quite certain that anyone exposed to concentrations remarkable higher than 16 mg BCl3/m³ will react to the burning/itching skin and respiratory sensation and will automatically start to wear PPE. If risk management measures are applied to prevent toxic effects by HCl then also the reproduction toxic effects of boric acid would be prevented.

The NOAECfertiliy = 340 mg BCl3/m³.

Endpoint conclusion:

adverse effect observed

Dose descriptor:

NOAEC

340 mg/m³

Study duration:

chronic

Species:

rat

Hydrogen chloride:

No reliable studies have been reported regarding toxicity to reproduction and development in animals after oral, dermal or inhalation exposure to hydrogen chloride/hydrochloric acid. Because protons and chloride ions are normal constituents in the body fluid of animal species, low concentrations of hydrogen chloride gas/mist or solution do not seem to cause adverse effects to animals. In fact, the cells of gastric glands secrete hydrochloric acid into the cavity of the stomach and orally administered sulfuric acid, which results in pH change as well, did not cause developmental toxicity to laboratory animals. These facts indicate that hydrogen chloride/hydrochloric acid is not expected to have developmental toxicity. In addition, no effects on the gonads were observed in a good quality 90-day inhalation study up to 50 ppm.

The local effects of HCl are predominant for repeated dose toxicity (including reproduction toxicity) compared to systemic effects, which as e.g. reduced body weight in 90-days toxicity studies are probably a sequel of the local effects. As reported under Section 7.5 a NOAEC of 15 mg HCl/m³, 6 h/d, 5 d/week, was derived from 90-day and 2-years inhalation toxicity studies. The NOAEC of 15 mg HCl/m³ correspond to 16 mg BCl3/m³ or to a NOAEL of 6.1 mg BCl3/kg bw/d.

Boric acid:

The second degradation product after BCl3 is coming into contact with water, i.e. boric acid, is classified under CLP as Repr. 1B, H360 FD. 'F' for fertility and 'D' for developmental toxicity. A classification as Repr. 1B, H360 FD is required for mixtures of boric acid at concentrations of ≥5.5 % which is remarkably higher for boric acid than the general concentration limit of 0.3 % v/v, set in Table 3.7.2 of Annex I of CLP. By setting this higher limit concentration it is expressed that the toxic effects of boric acid have a defined threshold and that the toxic effects are of lower concern, compared to other substances classified as Repr. 1B, H360 FD.

A series of studies, also on humans, are reported in the IUCLID for boric acid. An overall lowest NOAEL of 100 mg/kg bw/d is presented for fertility impairment, detected in a multigeneration study in rats, and a bench mark dose BMDL05 of 59 mg/kg bw/d is presented for developmental toxicity.

NOAELfertiliy = 100 mg B(OH)3/kg bw/d corresponds to 192 mg BCl3/kg bw/d. Converting the NOAELoral = 192 mg/kg bw to the more relevant inhalation exposure a NOAECinhal,8h/d = (192 mg/kg)/(0.38 m³/kg/d) * (6.7 m³/10 m³) * (100 %/100 %) = 340 mg BCl3/m³ is obtained. The conversion to a NOAEC was performed according to the ECHA Guidance on Info and CSA R.8 Figure R.8-3, assuming a workers exposure of 8 h/d and a 100 % absorption for inhalation and oral dosing and for rats and human. The 100 % absorptions are justified, see Section 7.1 on Toxicokinetics.

Endpoint conclusion:

It is concluded that the local toxic effects of HCl occur at concentrations of >16 mg BCl3/m³ whereas boric acid causes reproductive effects only at 21 times higher doses of >200 mg/kg bw/d. Reproductive effects therefore could only occur at doses already causing significant local toxic effects or in other words at maternal and paternal toxic doses. It is quite certain that anyone exposed to concentrations remarkable higher than 16 mg BCl3/m³ will react to the burning/itching skin and respiratory sensation and will automatically start to wear PPE. If risk management measures are applied to prevent toxic effects by HCl then also the reproduction toxic effects of boric acid would be prevented.

The NOAECfertiliy = 340 mg BCl3/m³.

For the practical exposure, the limit for BCl3 will be 16 mg/m³, based on its corrosivity.

Reference

Endpoint:

developmental toxicity

Type of information:

migrated information: read-across based on grouping of substances (category approach)

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: A degradation category approach is applied, based on the very rapid hydrolysis of boron trichloride. The description and justification of the category is presented in Section 13.

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Principles of method if other than guideline:

A category approach is applied.

Dose descriptor:

NOAEL

Effect level:

55 mg/kg bw/day

Based on:

other: Boric acid.

Basis for effect level:

other: developmental toxicity

Dose descriptor:

NOAEL

Effect level:

104 mg/kg bw/day

Based on:

other: BCl3, by transcribing from the NOEL of 55 mg/kg bw for boric acid.

Basis for effect level:

other: developmental toxicity

Dose descriptor:

NOAEC

Effect level:

183 mg/m³ air

Based on:

other: BCl3

Basis for effect level:

other: developmental toxicity

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:yes

Details on embryotoxic / teratogenic effects:
Relevant data was obtained from the most sensitive species rat, from the 3 species rat, mouse, rabbit used, and oral application of boric acid. The critical effects are decreased fetal body weight in rats, increased incidence of wavy ribs and short ribs.

Abnormalities:

not specified

Developmental effects observed:

not specified

Relevant information for the 2 degradation products:

Hydrogen chloride:

No reliable studies have been reported regarding toxicity to reproduction and development in animals after oral, dermal or inhalation exposure to hydrogen chloride/hydrochloric acid. Because protons and chloride ions are normal constituents in the body fluid of animal species, low concentrations of hydrogen chloride gas/mist or solution do not seem to cause adverse effects to animals. In fact, the cells of gastric glands secrete hydrochloric acid into the cavity of the stomach and orally administered sulfuric acid, which results in pH change as well, did not cause developmental toxicity to laboratory animals. These facts indicate that hydrogen chloride/hydrochloric acid is not expected to have developmental toxicity. In addition, no effects on the gonads were observed in a good quality 90 -day inhalation study up to 50 ppm.

The local effects of HCl are predominant for repeated dose toxicity (including reproduction toxicity) compared to systemic effects, which as e.g. reduced body weight in 90-days toxicity studies are probably a sequel of the local effects. As reported under Section 7.5 a NOAEC of 15 mg HCl/m³, 6 h/d, 5 d/week, was derived from 90-day and 2-years inhalation toxicity studies. The NOAEC of 15 mg HCl/m³ correspond to 16 mg BCl3/m³ or to a NOAEL of 6.1 mg BCl3/kg bw/d.

Boric acid:

The second degradation product after BCl3 is coming into contact with water, i.e. boric acid, is classified under CLP as Repr. 1B, H360 FD. 'F' for fertility and 'D' for developmental toxicity. A classification as Repr. 1B, H360 FD is required for mixtures of boric acid at concentrations of ≥5.5 % which is remarkably higher for boric acid than the general concentration limit of 0.3 % v/v, set in Table 3.7.2 of Annex I of CLP. By setting this higher limit concentration it is expressed that the toxic effects of boric acid have a defined threshold and that the toxic effects are of lower concern, compared to other substances classified as Repr. 1B, H360 FD.

A series of studies are reported in the IUCLID for boric acid. Relevant data was obtained from the most sensitive species rat (from the 3 species rat, mouse, rabbit used) and oral application of boric acid. The critical effects are decreased fetal body weight in rats, increased incidence of wavy ribs and short ribs. The NOAEL is 9.6 mg B/kg bw/d, corresponding to 55 mg B(OH)3/kg bw/d. The IUCLID for boric acid reports a BMD05 of 59 mg B(OH)3/kg bw/d instead of the NOAEL.

NOAELdevelopmental = 55 mg B(OH)3/kg bw/d corresponds to 104 mg BCl3/kg bw/d. Converting the NOAELoral = 104 mg/kg bw to the more relevant inhalation exposure, a NOAECinhal,8h/d = (104 mg/kg)/(0.38 m³/kg/d) * (6.7 m³/10 m³) * (100 %/100 %) = 183 mg BCl3/m³ is obtained. The conversion to a NOAEC was performed according to the ECHA Guidance on Info and CSA R.8 Figure R.8-3, assuming a workers exposure of 8 h/d and a 100 % absorption for inhalation and oral dosing and for rats and human. The 100 % absorptions are justified, see Section 7.1 on Toxicokinetics.

Endpoint conclusion:

It is concluded that the local toxic effects of HCl occur at concentrations of >16 mg BCl3/m³ whereas boric acid causes developmental toxicity effects only at 11 times higher doses of 183 mg BCl3/m³. Developmental toxicity effects therefore could only occur at doses already causing significant local toxic effects or in other words at maternal and paternal toxic doses. It is quite certain that anyone exposed to concentrations remarkable higher than 16 mg BCl3/m³ will react to the burning/itching skin and respiratory sensation and will automatically start to wear PPE. If risk management measures are applied to prevent toxic effects by HCl then also the reproduction toxic effects of boric acid would be prevented.

The NOAECdevelopmental = 183 mg BCl3/m³.

For the practical exposure, the limit for BCl3 will be 16 mg/m³, based on its corrosivity.

Conclusions:

It is concluded that the local toxic effects of HCl occur at concentrations of >16 mg BCl3/m³ whereas the other degradation product of BCl3, i.e. boric acid, causes developmental toxicity effects only at 11 times higher doses:
The NOAECdevelopmental = 183 mg BCl3/m³.

Executive summary:

A degradation category approach is applied, based on the very rapid and complete degradation (hydrolysis) of boron trichloride in water to form hydrochloric acid and boric acid. The description and justification of the category is presented in Section 13. The endpoint results of the degradation products are transcribed to boron trichloride.

Relevant information for the 2 degradation products:

Hydrogen chloride:

No reliable studies have been reported regarding toxicity to reproduction and development in animals after oral, dermal or inhalation exposure to hydrogen chloride/hydrochloric acid. Because protons and chloride ions are normal constituents in the body fluid of animal species, low concentrations of hydrogen chloride gas/mist or solution do not seem to cause adverse effects to animals. In fact, the cells of gastric glands secrete hydrochloric acid into the cavity of the stomach and orally administered sulfuric acid, which results in pH change as well, did not cause developmental toxicity to laboratory animals. These facts indicate that hydrogen chloride/hydrochloric acid is not expected to have developmental toxicity. In addition, no effects on the gonads were observed in a good quality 90 -day inhalation study up to 50 ppm.

The local effects of HCl are predominant for repeated dose toxicity (including reproduction toxicity) compared to systemic effects, which as e.g. reduced body weight in 90-days toxicity studies are probably a sequel of the local effects. As reported under Section 7.5 a NOAEC of 15 mg HCl/m³, 6 h/d, 5 d/week, was derived from 90-day and 2-years inhalation toxicity studies. The NOAEC of 15 mg HCl/m³ correspond to 16 mg BCl3/m³ or to a NOAEL of 6.1 mg BCl3/kg bw/d.

Boric acid:

The second degradation product after BCl3 is coming into contact with water, i.e. boric acid, is classified under CLP as Repr. 1B, H360 FD. 'F' for fertility and 'D' for developmental toxicity. A classification as Repr. 1B, H360 FD is required for mixtures of boric acid at concentrations of ≥5.5 % which is remarkably higher for boric acid than the general concentration limit of 0.3 % v/v, set in Table 3.7.2 of Annex I of CLP. By setting this higher limit concentration it is expressed that the toxic effects of boric acid have a defined threshold and that the toxic effects are of lower concern, compared to other substances classified as Repr. 1B, H360 FD.

A series of studies are reported in the IUCLID for boric acid. Relevant data was obtained from the most sensitive species rat (from the 3 species rat, mouse, rabbit used) and oral application of boric acid. The critical effects are decreased fetal body weight in rats, increased incidence of wavy ribs and short ribs. The NOAEL is 9.6 mg B/kg bw/d, corresponding to 55 mg B(OH)3/kg bw/d. The IUCLID for boric acid reports a BMD05 of 59 mg B(OH)3/kg bw/d instead of the NOAEL.

NOAELdevelopmental = 55 mg B(OH)3/kg bw/d corresponds to 104 mg BCl3/kg bw/d. Converting the NOAELoral = 104 mg/kg bw to the more relevant inhalation exposure, a NOAECinhal,8h/d = (104 mg/kg)/(0.38 m³/kg/d) * (6.7 m³/10 m³) * (100 %/100 %) = 183 mg BCl3/m³ is obtained. The conversion to a NOAEC was performed according to the ECHA Guidance on Info and CSA R.8 Figure R.8-3, assuming a workers exposure of 8 h/d and a 100 % absorption for inhalation and oral dosing and for rats and human. The 100 % absorptions are justified, see Section 7.1 on Toxicokinetics.

Endpoint conclusion:

It is concluded that the local toxic effects of HCl occur at concentrations of >16 mg BCl3/m³ whereas boric acid causes developmental toxicity effects only at 11 times higher doses of 183 mg BCl3/m³. Developmental toxicity effects therefore could only occur at doses already causing significant local toxic effects or in other words at maternal and paternal toxic doses. It is quite certain that anyone exposed to concentrations remarkable higher than 16 mg BCl3/m³ will react to the burning/itching skin and respiratory sensation and will automatically start to wear PPE. If risk management measures are applied to prevent toxic effects by HCl then also the reproduction toxic effects of boric acid would be prevented.

The NOAECdevelopmental = 183 mg BCl3/m³.

For the practical exposure, the limit for BCl3 will be 16 mg/m³, based on its corrosivity.

Endpoint conclusion:

adverse effect observed

Dose descriptor:

NOAEC

183 mg/m³

Species:

rat

Hydrogen chloride:

No reliable studies have been reported regarding toxicity to reproduction and development in animals after oral, dermal or inhalation exposure to hydrogen chloride/hydrochloric acid. Because protons and chloride ions are normal constituents in the body fluid of animal species, low concentrations of hydrogen chloride gas/mist or solution do not seem to cause adverse effects to animals. In fact, the cells of gastric glands secrete hydrochloric acid into the cavity of the stomach and orally administered sulfuric acid, which results in pH change as well, did not cause developmental toxicity to laboratory animals. These facts indicate that hydrogen chloride/hydrochloric acid is not expected to have developmental toxicity. In addition, no effects on the gonads were observed in a good quality 90 -day inhalation study up to 50 ppm.

The local effects of HCl are predominant for repeated dose toxicity (including reproduction toxicity) compared to systemic effects, which as e.g. reduced body weight in 90-days toxicity studies are probably a sequel of the local effects. As reported under Section 7.5 a NOAEC of 15 mg HCl/m³, 6 h/d, 5 d/week, was derived from 90-day and 2-years inhalation toxicity studies. The NOAEC of 15 mg HCl/m³ correspond to 16 mg BCl3/m³ or to a NOAEL of 6.1 mg BCl3/kg bw/d.

Boric acid:

The second degradation product after BCl3 is coming into contact with water, i.e. boric acid, is classified under CLP as Repr. 1B, H360 FD. 'F' for fertility and 'D' for developmental toxicity. A classification as Repr. 1B, H360 FD is required for mixtures of boric acid at concentrations of ≥5.5 % which is remarkably higher for boric acid than the general concentration limit of 0.3 % v/v, set in Table 3.7.2 of Annex I of CLP. By setting this higher limit concentration it is expressed that the toxic effects of boric acid have a defined threshold and that the toxic effects are of lower concern, compared to other substances classified as Repr. 1B, H360 FD.

A series of studies are reported in the IUCLID for boric acid. Relevant data was obtained from the most sensitive species rat (from the 3 species rat, mouse, rabbit used) and oral application of boric acid. The critical effects are decreased fetal body weight in rats, increased incidence of wavy ribs and short ribs. The NOAEL is 9.6 mg B/kg bw/d, corresponding to 55 mg B(OH)3/kg bw/d. The IUCLID for boric acid reports a BMD05 of 59 mg B(OH)3/kg bw/d instead of the NOAEL.

NOAELdevelopmental = 55 mg B(OH)3/kg bw/d corresponds to 104 mg BCl3/kg bw/d. Converting the NOAELoral = 104 mg/kg bw to the more relevant inhalation exposure, a NOAECinhal,8h/d = (104 mg/kg)/(0.38 m³/kg/d) * (6.7 m³/10 m³) * (100 %/100 %) = 183 mg BCl3/m³ is obtained. The conversion to a NOAEC was performed according to the ECHA Guidance on Info and CSA R.8 Figure R.8-3, assuming a workers exposure of 8 h/d and a 100 % absorption for inhalation and oral dosing and for rats and human. The 100 % absorptions are justified, see Section 7.1 on Toxicokinetics.

Endpoint conclusion:

It is concluded that the local toxic effects of HCl occur at concentrations of >16 mg BCl3/m³ whereas boric acid causes developmental toxicity effects only at 11 times higher doses of 183 mg BCl3/m³. Developmental toxicity effects therefore could only occur at doses already causing significant local toxic effects or in other words at maternal and paternal toxic doses. It is quite certain that anyone exposed to concentrations remarkable higher than 16 mg BCl3/m³ will react to the burning/itching skin and respiratory sensation and will automatically start to wear PPE. If risk management measures are applied to prevent toxic effects by HCl then also the reproduction toxic effects of boric acid would be prevented.

The NOAECdevelopmental = 183 mg BCl3/m³.

For the practical exposure, the limit for BCl3 will be 16 mg/m³, based on its corrosivity.

No classification in Repr. xx is proposed for BCl3, because the toxic effects of HCl predominate the possible effects of B(OH)3. The latter could only occur at doses or concentrations leading already to corrosive effects by HCl.

Reproductive effects therefore occur only at doses already causing significant local toxic effects or in other words at maternal and paternal toxic doses. It is most likely that anyone exposed to concentrations remarkably higher than 16 mg BCl3/m³ will react to the burning/itching skin sensation and will automatically start to wear PPE. If risk management measures are applied to prevent toxic effects caused by the produced HCl then also the reproductive toxic effects of boric acid would be prevented.