Registration Dossier

BCl3 is corrosive to skin.

The 2 relevant NOAEC for BCl3, transcribed from the results of the 2 degradation products are:

- 16 mg BCl3/m³ based on 90d and on 2-years inhalation studies with HCl exposure for 6 h/d and 5 d/week to rats.

- 340 mg BCl3/m³ based on two oral 2-years studies with rats and mice with boric acid, and converted to a NOAEC, 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.

Boric acid is less toxic by a factor of >20, compared to HCl. The lower of the 2 NOAECs is critical for the BCl3 hazard evaluation. Therefore:

NOAECrat,6h/d,5d/w = 16 mg BCl3/m³ based on a 2-years inhalation study.

The corrected NOAEC for worker conditions is NOAEC8h/d,5d/w = 8 mg BCl3/m³.

Data on the human health effects are generally limited to poorly reported secondary sources. Exposure of male volunteers to 50 - 100 ppm (76 - 152 mg/m3) hydrogen chloride gas for 1 hour was claimed to be barely tolerable (Henderson and Haggard, 1943). Irritation of the throat resulted from brief exposure to 35 ppm (53 mg/m3) and 10 ppm (15 mg/m3) was considered to be the maximal acceptable concentration for prolonged exposure. This is in reasonable agreement with the animal data, and a useful NOAEC of 16 mg BCl3/m³.

Based on possible long-term effects, the SCOEL recommends for HCl a TWA 8 hour of 5 ppm (8 mg HCl/m3). This value will be used as DNEL for long term inhalation exposure of HCl. Transcription to BCl3 gives a TWA8h = 8.6 mg BCl3/m³, in good agreement with the NOAEC for workers, see above.

Reference

Endpoint:

short-term repeated dose toxicity: oral

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Justification for type of information:

Hydrogen chloride:
A study is not required, nor considered an appropriate use of animals because of the known effects of presence of hydrogen chloride in the GI tract. The chemistry of this substance is well understood; as an inorganic salt it dissolves in water to form hydrogen and chloride ions, both of which are physiological electrolytes. Concentrated hydrogen chloride is corrosive to biological tissues. At concentrations lower than those that cause corrosion or irritancy, hydrogen chloride will have no effect on systemic toxicity. Following oral exposure, passage through the stomach will merely add modestly to the hydrochloric acid already present in the stomach. As a result of the physiological presence of hydrochloric acid in the stomach, the effects of excess (or insufficient) hydrogen chloride by the oral route are well understood. No further animal testing is necessary, or appropriate.

Boric acid:
A number of sub-chronic and chronic studies on boric acid and on disodium tetraborate were carried out in rats, mice and dogs. Most support that boron can cause adverse haematological effects and that the main target organ of boron toxicity is the testis. The NOAEL is 100 mg/kg bw/d for boric acid, from the chronic oral study with rat.

Principles of method if other than guideline:

A category approach is applied.

Route of administration:

oral: unspecified

Details on results:

Hydrogen chloride:
A study is not required, nor considered an appropriate use of animals because of the known effects of presence of hydrogen chloride in the GI tract. The chemistry of this substance is well understood; as an inorganic salt it dissolves in water to form hydrogen and chloride ions, both of which are physiological electrolytes. Concentrated hydrogen chloride is corrosive to biological tissues. At concentrations lower than those that cause corrosion or irritancy, hydrogen chloride will have no effect on systemic toxicity. Following oral exposure, passage through the stomach will merely add modestly to the hydrochloric acid already present in the stomach. As a result of the physiological presence of hydrochloric acid in the stomach, the effects of excess (or insufficient) hydrogen chloride by the oral route are well understood. No further animal testing is necessary, or appropriate.

Boric acid:
A number of sub-chronic and chronic studies on boric acid and on disodium tetraborate were carried out in rats, mice and dogs. Most support that boron can cause adverse haematological effects and that the main target organ of boron toxicity is the testis. The NOAEL is 100 mg/kg bw/d for boric acid, from the chronic oral study with rat.

Critical effects observed:

not specified

Conclusions:

The likely route of exposure for this gas is inhalation, and a read across to a repeated dose study by inhalation is provided and considered relevant and appropriate to address the anticipated route of human exposure.

Executive summary:

The likely route of exposure for this gas is inhalation, and a read across to a repeated dose study by inhalation is provided and considered relevant and appropriate to address the anticipated route of human exposure.

Read across to data for the 2 degradation products:

Hydrogen chloride:

A study is not required, nor considered an appropriate use of animals because of the known effects of presence of hydrogen chloride in the GI tract. The chemistry of this substance is well understood; as an inorganic salt it dissolves in water to form hydrogen and chloride ions, both of which are physiological electrolytes. Concentrated hydrogen chloride is corrosive to biological tissues. At concentrations lower than those that cause corrosion or irritancy, hydrogen chloride will have no effect on systemic toxicity. Following oral exposure, passage through the stomach will merely add modestly to the hydrochloric acid already present in the stomach. As a result of the physiological presence of hydrochloric acid in the stomach, the effects of excess (or insufficient) hydrogen chloride by the oral route are well understood. No further animal testing is necessary, or appropriate.

Boric acid:

A number of sub-chronic and chronic studies on boric acid and on disodium tetraborate were carried out in rats, mice and dogs. Most support that boron can cause adverse haematological effects and that the main target organ of boron toxicity is the testis. The NOAEL is 100 mg/kg bw/d for boric acid, from the chronic oral study with rat.

Reference

Endpoint:

short-term repeated dose toxicity: inhalation

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Justification for type of information:

The 2 relevant NOAEC for BCl3, transcribed from the results of the 2 degradation products are:
- 16 mg BCl3/m³ based on 90d and on 2-years inhalation studies with HCl exposure for 6 h/d and 5 d/week to rats.
- 340 mg BCl3/m³ based on two oral 2-years studies with rats and mice with boric acid, and converted to a NOAEC, 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.

Boric acid is less toxic by a factor of >20, compared to HCl. The lower of the 2 NOAECs is critical for the BCl3 hazard evaluation. Therefore:
NOAECrat,6h/d,5d/w = 16 mg BCl3/m³ based on a 2-years inhalation study. This NOAEC was further converted to an exposure duration of 8 h/d for workers and an increased respiratory volume of workers. NOAECworkers,8h/d,5d/w = 16 mg BCl3/m³ *(6/8) * 6.7/10) = 8 mg/m³.

Principles of method if other than guideline:

A category approach is applied.

Route of administration:

inhalation

Details on results:

The 2 relevant NOAEC for BCl3, transcribed from the results of the 2 degradation products are:
- 16 mg BCl3/m³ based on 90d and on 2-years inhalation studies with HCl exposure for 6 h/d and 5 d/week to rats.
- 340 mg BCl3/m³ based on two oral 2-years studies with rats and mice with boric acid, and converted to a NOAEC, 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.

Boric acid is less toxic by a factor of >20, compared to HCl. The lower of the 2 NOAECs is critical for the BCl3 hazard evaluation. Therefore:
NOAECrat,6h/d,5d/w = 16 mg BCl3/m³ based on a 2-years inhalation study. This NOAEC was further converted to an exposure duration of 8 h/d for workers and an increased respiratory volume of workers. NOAECworkers,8h/d,5d/w = 16 mg BCl3/m³ *(6/8) * 6.7/10) = 8 mg/m³.

Dose descriptor:

NOAEC

Effect level:

15 mg/m³ air

Based on:

other: hydrogen chloride

Sex:

male/female

Basis for effect level:

other: see 'Remark'

Dose descriptor:

NOAEC

Effect level:

15 mg/m³ air

Based on:

other: hydrogen chloride

Sex:

male/female

Basis for effect level:

other: see 'Remark'

Dose descriptor:

NOAEC

Effect level:

16 mg/m³ air

Based on:

other: BCl3 by transcribing from the 2 NOAECs of 15 mg/m³ for HCl

Sex:

male/female

Dose descriptor:

NOAEL

Effect level:

100 mg/kg bw/day (actual dose received)

Based on:

other: boric acid.

Sex:

male/female

Basis for effect level:

other: The NOAEL of 100 mg/kg bw is based on two 2-years studies with rats and mice with boric acid and disodium tetraborate. Effects were observed in testes and the blood system.

Dose descriptor:

NOAEL

Effect level:

192 mg/kg bw/day (actual dose received)

Based on:

other: BCl3 by transcribing from the NOEL of 100 mg/kg bw for boric acid.

Sex:

male/female

Dose descriptor:

NOAEC

Effect level:

340 mg/m³ air

Based on:

other: BCl3

Sex:

male/female

Basis for effect level:

other: see 'Remark'

Critical effects observed:

not specified

Conclusions:

The corrected NOAEC for worker conditions is NOAEC8h/d,5d/w = 8 mg/m³ based on a 2-years inhalation study.

Executive summary:

The 2 relevant NOAEC for BCl3, transcribed from the results of the 2 degradation products are:

- 16 mg BCl3/m³ based on 90d and on 2-years inhalation studies with HCl exposure for 6 h/d and 5 d/week to rats.

- 340 mg BCl3/m³ based on two oral 2-years studies with rats and mice with boric acid, and converted to a NOAEC, 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.

Boric acid is less toxic by a factor of >20, compared to HCl. The lower of the 2 NOAECs is critical for the BCl3 hazard evaluation. Therefore:

NOAECrat,6h/d,5d/w = 16 mg BCl3/m³ based on a 2-years inhalation study.

The corrected NOAEC for worker conditions is NOAEC8h/d,5d/w = 8 mg BCl3/m³.

Endpoint conclusion:

adverse effect observed

Dose descriptor:

NOAEC

16 mg/m³

Study duration:

subchronic

Species:

rat

Quality of whole database:

Guideline study with GLP.

Reference

Endpoint:

short-term repeated dose toxicity: inhalation

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Justification for type of information:

The 2 relevant NOAEC for BCl3, transcribed from the results of the 2 degradation products are:
- 16 mg BCl3/m³ based on 90d and on 2-years inhalation studies with HCl exposure for 6 h/d and 5 d/week to rats.
- 340 mg BCl3/m³ based on two oral 2-years studies with rats and mice with boric acid, and converted to a NOAEC, 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.

Boric acid is less toxic by a factor of >20, compared to HCl. The lower of the 2 NOAECs is critical for the BCl3 hazard evaluation. Therefore:
NOAECrat,6h/d,5d/w = 16 mg BCl3/m³ based on a 2-years inhalation study. This NOAEC was further converted to an exposure duration of 8 h/d for workers and an increased respiratory volume of workers. NOAECworkers,8h/d,5d/w = 16 mg BCl3/m³ *(6/8) * 6.7/10) = 8 mg/m³.

Principles of method if other than guideline:

A category approach is applied.

Route of administration:

inhalation

Details on results:

The 2 relevant NOAEC for BCl3, transcribed from the results of the 2 degradation products are:
- 16 mg BCl3/m³ based on 90d and on 2-years inhalation studies with HCl exposure for 6 h/d and 5 d/week to rats.
- 340 mg BCl3/m³ based on two oral 2-years studies with rats and mice with boric acid, and converted to a NOAEC, 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.

Boric acid is less toxic by a factor of >20, compared to HCl. The lower of the 2 NOAECs is critical for the BCl3 hazard evaluation. Therefore:
NOAECrat,6h/d,5d/w = 16 mg BCl3/m³ based on a 2-years inhalation study. This NOAEC was further converted to an exposure duration of 8 h/d for workers and an increased respiratory volume of workers. NOAECworkers,8h/d,5d/w = 16 mg BCl3/m³ *(6/8) * 6.7/10) = 8 mg/m³.

Dose descriptor:

NOAEC

Effect level:

15 mg/m³ air

Based on:

other: hydrogen chloride

Sex:

male/female

Basis for effect level:

other: see 'Remark'

Dose descriptor:

NOAEC

Effect level:

15 mg/m³ air

Based on:

other: hydrogen chloride

Sex:

male/female

Basis for effect level:

other: see 'Remark'

Dose descriptor:

NOAEC

Effect level:

16 mg/m³ air

Based on:

other: BCl3 by transcribing from the 2 NOAECs of 15 mg/m³ for HCl

Sex:

male/female

Dose descriptor:

NOAEL

Effect level:

100 mg/kg bw/day (actual dose received)

Based on:

other: boric acid.

Sex:

male/female

Basis for effect level:

other: The NOAEL of 100 mg/kg bw is based on two 2-years studies with rats and mice with boric acid and disodium tetraborate. Effects were observed in testes and the blood system.

Dose descriptor:

NOAEL

Effect level:

192 mg/kg bw/day (actual dose received)

Based on:

other: BCl3 by transcribing from the NOEL of 100 mg/kg bw for boric acid.

Sex:

male/female

Dose descriptor:

NOAEC

Effect level:

340 mg/m³ air

Based on:

other: BCl3

Sex:

male/female

Basis for effect level:

other: see 'Remark'

Critical effects observed:

not specified

Conclusions:

The corrected NOAEC for worker conditions is NOAEC8h/d,5d/w = 8 mg/m³ based on a 2-years inhalation study.

Executive summary:

The 2 relevant NOAEC for BCl3, transcribed from the results of the 2 degradation products are:

- 16 mg BCl3/m³ based on 90d and on 2-years inhalation studies with HCl exposure for 6 h/d and 5 d/week to rats.

- 340 mg BCl3/m³ based on two oral 2-years studies with rats and mice with boric acid, and converted to a NOAEC, 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.

Boric acid is less toxic by a factor of >20, compared to HCl. The lower of the 2 NOAECs is critical for the BCl3 hazard evaluation. Therefore:

NOAECrat,6h/d,5d/w = 16 mg BCl3/m³ based on a 2-years inhalation study.

The corrected NOAEC for worker conditions is NOAEC8h/d,5d/w = 8 mg BCl3/m³.

Endpoint conclusion:

adverse effect observed

Dose descriptor:

NOAEC

16 mg/m³

Study duration:

subchronic

Species:

rat

Quality of whole database:

Guideline study with GLP.

Reference

Endpoint:: short-term repeated dose toxicity: dermal
Data waiving:: study scientifically not necessary / other information available
Justification for data waiving:: other:
Critical effects observed:: not specified
Conclusions:: The likely route of exposure for this gas is inhalation, and a read across to a repeated dose study by inhalation is provided and considered relevant and appropriate to address the anticipated route of human exposure.
Executive summary:: The likely route of exposure for this gas is inhalation, and a read across to a repeated dose study by inhalation is provided and considered relevant and appropriate to address the anticipated route of human exposure.

Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:

The likely route of exposure for this gas is inhalation, and a read across to a repeated dose study by inhalation is provided and considered relevant and appropriate to address the anticipated route of human exposure.

Justification for selection of repeated dose toxicity dermal - systemic effects endpoint:

The likely route of exposure for this gas is inhalation, and a read across to a repeated dose study by inhalation is provided and considered relevant and appropriate to address the anticipated route of human exposure.

The substance is corrosive to skin.

Repeated dose toxicity: inhalation - systemic effects (target organ) other: skin

Repeated dose toxicity: dermal - systemic effects (target organ) other: skin

Derived from the more relevant degradation product HCl: The only observed lesions were local, corrosive effects and sequels as body weight changes. The corrosive effects of HCl and of BCl3 are known and are covered by the classification of both substances as corrosive. No justification is therefore obtained to classify BCl3 according to a specific target organ toxicity.

The NOAELoral for the other degradation product, boric acid, is 100 mg/kg bw from a 2-years study with rats, and therefore does not justify a classification, too.