[No public or meaningful name is available]

Direct observations: clinical cases, poisoning incidents and other

Administrative data

Endpoint:

direct observations: clinical cases, poisoning incidents and other

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

supporting study

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
In this read-across approach data on borates and boric oxides are used to fill data gaps for boric acid, in accordance with Regulation No 1907/2006 (REACH), Annex XI. The basis for this read-across approach is the “Read-Across Assessment Framework” (RAAF) (ECHA 2017). The read-across hypothesis for the analogue approach is that boric acid and borates as well as boron oxides exhibit a similar (eco)toxicological profile. This is due to the fact, that undissociated boric acid (B(OH)3) is the predominant species in near neutral pH, regardless of whether the boron source is boric acid or one of the borates (IPCS, 1998). Thus, different borates and boric oxides are used for hazard assessment. According to the RAAF this approach is covered by scenario 1: “(Bio)transformation to common compound(s)”.
“This scenario covers the analogue approach for which the read-across hypothesis is based on (bio) transformation to common compound(s). For the REACH information requirement under consideration, the property investigated in a study conducted with one source substance is used to predict the properties that would be observed in a study with the target substance if it were to be conducted. Similar properties or absence of effect are predicted. The predicted property may be similar or based on a worst-case approach.” (ECHA 2017).

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
Source chemicals:
Borax (Sodium borate / Disodium tetraborate / Disodium tetraborate decahydrate, Sodium tetraborate pentahydrate 1330-43-4/ 1303-96-4/ 12179-04-3)
Sodium pentaborate decahydrate (12046-75-2), Sodium metaborate, anhydrous (7775-19-1), Pentaboron sodium octaoxide (12007-92-0)
Borane (7440-42-8)
Boric oxide, bicyclo[1.1.1]diboroxane (Diboron trioxide, 1303-86-2)
Target chemical:
Boric acid (10043-35-3)

3. ANALOGUE APPROACH JUSTIFICATION
In aqueous solutions at physiological and environmentally relevant concentrations and pH ranges undissociated boric acid (B(OH)3) is the predominant species in near neutral pH found in most biological fluids, regardless of whether the boron source is boric acid or one of the borates. This is because boric acid is a very weak acid (pK. 9.15). Above pH 10 the metaborate anion B(OH)4- becomes the main species in solution. At higher boron concentrations ([B] > 0.025 M), polynuclear anionic complexes may be formed (IPCS, 1998). Regarding borane (BH3), aqueous solutions are extremely unstable, rapidly forming boric acid. Furthermore, boric oxide will exhibit properties identical to those of boric acid, as it is an anhydride that will hydrolyse to give boric acid (IPCS, 1998). The dissolution from simple borates to boric acid takes about 15 min. Based on the fact that in the environment and in biological fluids the same compounds are formed from the source and the target substances, the same (eco)toxicological profile of boric acid and borates as well as boric oxides is expected. Therefore, the read-across approach is justified. Thus, the available studies for source substances borates and boron oxides were used to fill data gaps for boric acid for several environmental and toxicological endpoints.

Cross-reference

Reason / purpose for cross-reference:

read-across source

Reference

Endpoint:

direct observations: clinical cases, poisoning incidents and other

Type of information:

other: Case study.

Adequacy of study:

supporting study

Study period:

No data

Reliability:

other: Not applicable this is a case study.

Rationale for reliability incl. deficiencies:

other: Not applicable this is a case study.

Study type:

clinical case study

Endpoint addressed:

repeated dose toxicity: inhalation

Qualifier:

no guideline followed

Principles of method if other than guideline:

The reference describes a clinical case study in humans.

GLP compliance:

no

Subjects:

- Number of subjects exposed: 1
- Sex: Male
- Age: 50

Route of exposure:

inhalation

Reason of exposure:

unintentional, occupational

Exposure assessment:

estimated

Clinical signs:

A man of 50 years presented alopecia due to occupational contact with borax. The man presented who the dermatological policlinc with the complaint that in the last week his scalp hair had fallen out very markedly during washing. He reported that increased loss of hair had been observed for 3 months, most marked shortly before he attended the clinic. He also had other complaints. 6 months previously he had felt very nervous and excited, suffered from insomnia and attacks of headache with pyrexia and frequent muscle pains, especially in the extremities. A week after the increased loss of hair, his face and head grew red and flaky. On examination the patient was observed in moderately good health, but somewhat lean. The most striking feature was the diffuse loss of hair, the alopecia being most marked in the medial region of the head. The bear growth had decreased markedly in the previous few weeks. The skin of the face and head exhibited a slightly diffuse which desquamation against an erythematous background with a psoriasiform aspect. He had no gastrointestinal disorder, no nausea or vomiting, although his appetite had decreased. There was no marked loss of body weight.There was no hepatic or renal disease and no psychiatric disorder. The blood picture and SR were normal. The Wassermann test was negative. His occupation was as a storekeeper and one of his duties was to fill a dispenser with washing powder almost daily, which he had done for more than 6 years. The washing powder was stored in a drum with a capacity of 50 kg in a store room with almost mo ventilation. The washing powder was finely granular and the patient frequently sneezed several times during this task of filling the dispenser as he could not avoid inhaling some of it. The patient was subsequently asked to avoid all contact with the washing powder and all symptoms including loss of hair subsided. 6 weeks following discontinuation boron was demonstrated in the urine, which was acidified with dilute HCl and concentrated by evaporation and tested using turmeric paper. A few months later when the patient’s hair growth was more or less normal the urine was once again tested for borax and was negative.

Conclusions:

A man of 50 years presented alopecia due to occupational contact with borax. The man presented who the dermatological policlinc with the complaint that in the last week his scalp hair had fallen out very markedly during washing. He reported that increased loss of hair had been observed for 3 months, most marked shortly before he attended the clinic. The diagnosis was of alopecia after toxic agent.

Materials and methods

Test material

Test material information

Constituent 1

Reference substance name:

Boric acid

EC Number:

233-139-2

EC Name:

Boric acid

Cas Number:

10043-35-3

Molecular formula:

H3BO3

IUPAC Name:

Boric acid

Results and discussion

Clinical signs:

A man of 50 years presented alopecia due to occupational contact with borax. The man presented who the dermatological policlinc with the complaint that in the last week his scalp hair had fallen out very markedly during washing. He reported that increased loss of hair had been observed for 3 months, most marked shortly before he attended the clinic. He also had other complaints. 6 months previously he had felt very nervous and excited, suffered from insomnia and attacks of headache with pyrexia and frequent muscle pains, especially in the extremities. A week after the increased loss of hair, his face and head grew red and flaky. On examination the patient was observed in moderately good health, but somewhat lean. The most striking feature was the diffuse loss of hair, the alopecia being most marked in the medial region of the head. The bear growth had decreased markedly in the previous few weeks. The skin of the face and head exhibited a slightly diffuse which desquamation against an erythematous background with a psoriasiform aspect. He had no gastrointestinal disorder, no nausea or vomiting, although his appetite had decreased. There was no marked loss of body weight.There was no hepatic or renal disease and no psychiatric disorder. The blood picture and SR were normal. The Wassermann test was negative. His occupation was as a storekeeper and one of his duties was to fill a dispenser with washing powder almost daily, which he had done for more than 6 years. The washing powder was stored in a drum with a capacity of 50 kg in a store room with almost mo ventilation. The washing powder was finely granular and the patient frequently sneezed several times during this task of filling the dispenser as he could not avoid inhaling some of it. The patient was subsequently asked to avoid all contact with the washing powder and all symptoms including loss of hair subsided. 6 weeks following discontinuation boron was demonstrated in the urine, which was acidified with dilute HCl and concentrated by evaporation and tested using turmeric paper. A few months later when the patient’s hair growth was more or less normal the urine was once again tested for borax and was negative.

Applicant's summary and conclusion

Conclusions:

A man of 50 years presented alopecia due to occupational contact with borax. The man presented who the dermatological policlinc with the complaint that in the last week his scalp hair had fallen out very markedly during washing. He reported that increased loss of hair had been observed for 3 months, most marked shortly before he attended the clinic. The diagnosis was of alopecia after toxic agent.