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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
5.5 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
12.5
Modified dose descriptor starting point:
NOAEC
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
258 mg/kg bw/day
Most sensitive endpoint:
developmental toxicity / teratogenicity
DNEL related information
Overall assessment factor (AF):
30
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

Worker-DNELlong-term, inhalation, systemic


This route is not relevant for systemic effects in the general population, but in the occupational setting considerable boron dust concentrations may arise.


The oral BMDL05 of 10.3 mg B/kg bw/day was used as starting point based on the most critical endpoint (development) and corrected considering an eight-hour workday and a respiratory volume of 10 m3. The corrected inhalation NOAEC of 18.16 mg B/m3 was calculated as recommended by Chapter R.8 from the Guidance on IR and CSA using the following equation:


Corrected Inhalation NOAEC = oral BMDL05x (1/ sRVrat) x (ABSoral-rat/ ABSinh-rat) x (sRVhuman/ wRV)


Corrected Inhalation NOAEC = 10.3 mg B/kg bw/day x (1/ 0.38 m3/d) x (100 %/ 100 %) x (6.7 m3(8h) / 10 m3(8h))


Corrected Inhalation NOAEC = 18.16 mg B/m3


sRV: standard Respiratory Volume


ABS: Absorption


wRV: worker Respiratory Volume


sRVrat= 0.38 m3/day


sRVhuman= 6.7 m3/day (8h)


sRVhuman, moderate work= 10 m3/day (8h)


ABSoral-rat= ABSinh-human= 100 %


 


Absorption of boric acid and tetraborates via the oral route is close to 100 %. Due to the good water solubility of the compounds and studies in animals and humans a realistic worst case assumption of 100 % absorption via the inhalation route is justified. Borates exist predominantly as un-dissociated boric acid in dilute aqueous solution at physiological pH, it is not further metabolized, therefore it can be concluded that the main species in the plasma of mammals is un-dissociated boric acid, and as such can exert its toxic effects in the target organs. The toxicokinetics of boric acid and disodium tetraborates are similar in rats and humans with regard to absorption, distribution, and metabolism. Differences exist for renal clearance, which is approximately 3 times faster in rats compared to humans. The physiological process of renal clearance is affected by the basal metabolic rate. In the above stated formular differences with regard to metabolic rate between rats and humans are considered. The remaining inter-species differences are covered by applying the factor 2.5 for toxicodynamic differences. An additional factor for uncertainties caused by route-to-route extrapolation was considered not necessary.


Worker-DNELlong-term, inhalation, systemic= (18.16 mg B/m3) / (2.5 x 5) =1.45 mg B/m3 or:


Sodium pentaborate (anhydrous): 5.5 mg/m³


Sodium pentaborate (pentahydrate): 7.9 mg/m³


 


Worker-DNELlong-term, dermal, systemic


For risk assessment of borates a dermal absorption of 0.5 % is used as a worst case approach. Dermal absorption is not regarded relevant for the general population, however, it is considered for workers. A Worker-DNELlong-term, dermal, systemic is derived from the oral BMDL05 of 10.3 mg B/kg bw/day. The assessment factors applied are for interspecies variability (5) and intraspecies variability (6). A DNEL of 0.34 mg B/kg bw/day was obtained for workers. A body weight for workers of 70 kg was assumed.


 


Worker-DNELlong-term, dermal, systemic = (10.3 mg B/kg bw/day) / (6 x 5) = 0.34 mg B/kg bw/day or:


 


Sodium pentaborate (anhydrous): 1.3 mg/kg bw/day


Sodium pentaborate (pentahydrate): 1.8 mg/kg bw/day


 


External DNEL value = (0.34 mg B/kg bw/day)/0.5% dermal absorption value = 68 mg B/kg bw/day or:


 


Sodium pentaborate (anhydrous): 258 mg/kg bw/day


Sodium pentaborate (pentahydrate): 371.2 mg/kg bw/day

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.75 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
25
Modified dose descriptor starting point:
NOAEC
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
9.6 mg/m³
Most sensitive endpoint:
irritation (respiratory tract)
DNEL related information
Dose descriptor:
NOAEC
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
129 mg/kg bw/day
Most sensitive endpoint:
developmental toxicity / teratogenicity
DNEL related information
Overall assessment factor (AF):
60
Modified dose descriptor starting point:
BMDL05
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.64 mg/kg bw/day
Most sensitive endpoint:
developmental toxicity / teratogenicity
DNEL related information
Overall assessment factor (AF):
60
Modified dose descriptor starting point:
BMDL05
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

General population DNELlong-term, oral, systemic


With regard to developmental effects no human data exist. The available data from animal studies are sufficient to conclude that prenatal exposure to boron (specifically boric acid and disodium tetraborates) by the oral route can cause developmental toxicity. Developmental effects were seen in three different mammalian species, rat, mouse and rabbit, with the rat being most sensitive. From the most robust study in rats (Price et al., 1996) the lowest NOAEL = 9.6 mg B/kg bw/day can be derived for reduced foetal body weight per litter, increase in wavy ribs and increased incidence in short rib XIII. Other effects seen at maternally toxic doses were visceral malformations like enlarged ventricles and cardiovascular effects.


Several epidemiological studies on fertility effects of borates have been carried out in workers and populations living in areas with high environmental levels of boron (Truhaut et al., 1964, Tarasenko, 1972, Krasovskii et al., 1976, Whorton, 1994, Tuccar, 1998 and Sayli, 1998, 2001, 2003).


In general, the need for good epidemiological studies on male and female fertility, as well as on developmental toxicity was clearly identified by several national and international panels (BfR, 2005; EFSA, 2004; Commission Working, 2004; WHO, 1998; ECETOC, 1995; US EPA, 2004).


Male infertility was observed in breeding studies in rats, mice and deer mice. The underlying cause for male infertility was identified to be testicular atrophy. A series of studies has been published that provide insight as to the mechanistic nature of the lesion in rats. Good correlation between doses inducing spermatogenic arrest and infertility could be derived. The effects were reversible at lower doses, but no recovery was possible at doses at which germ cell loss was observed. Germinal depletion correlated well with increased plasma levels of FSH. Levels of other hormones, like testosterone and LH were not always affected. A NOAEL of 17.5 mg B/kg bw/day in rats (Weir, 1966a, b) could be derived.


Two 3-generation studies in rats with boric acid and disodium tetraborate decahydrate (Weir, 1966c, d) and a continuous breeding study in mice with boric acid (Fail et al., 1991) further substantiate the effects seen in males.


The NOAEL of 9.6 mg/kg body weight per day is based on the critical developmental effect of decreased fetal body weight in rats. Allen et al. (1996) developed a benchmark dose based on the studies of Heindel et al. (1992), Price, Marr & Myers (1994) and Price et al. (1996a). The benchmark dose is defined as the 95% lower bound on the dose corresponding to a 5% decrease in the mean fetal weight (BMDL05) and was used by the United States Environmental Protection Agency in its re-evaluation (USEPA, 2004) and by WHO in its guideline for boron in drinking water (2009). The BMDL05 of 10.3 mg/kg body weight per day as boron is close to the Price et al. (1996a) NOAEL of 9.6 mg/kg body weight per day. The uncertainty factor used by WHO was derived following the methodology of Doursen et al. (1998).


The most appropriate TK uncertainty factor for intraspecies variability is based on available data in pregnant humans for variation in glomerular filtration rate (GFR) as a surrogate for the clearance and elimination of B. This choice is most appropriate because the pregnant human is the population associated with B's critical effect. Furthermore, B's elimination is the kinetic area with the most variability, absorption and distribution of B are expected to be very similar among humans and B is not metabolized. Based on division of the mean glomerular filtration rate by the glomerular filtration rate at two standard deviations below the mean to address variability for approximately 95 % of the population, the toxicokinetic component of interspecies variation is 1.8 (compared with the default value for this component of 3.2). As there are insufficient data to serve as a basis for replacement of the default value for the toxicodynamic component of the uncertainty factor for intraspecies variation, the total uncertainty factor for intraspecies variation is 1.8 x 3.2 = 5.76 (rounded to 6). Data are inadequate to determine a different uncertainty factor for interspecies variation; therefore, the default value of 10 is used (Doursen et al., 1998), giving a total uncertainty factor of 60. The appropriate uncertainty factor for other areas of uncertainty, and specifically for database uncertainty, is 1-fold.


The uncertainty factor (UF) of 60 used in derivation of the DNEL is more conservative than UFs previously used by several other national and international panels where UFs ranging from 25 to 30 have been used (IEHR 1995, ECETOC 1995, IPCS 1998, NAS FNB 2000; See Appendix E). The default factor of 100 (10 x 10) was used under the Biocidal Products Directive in 2009, and a total UF of 150 for the general population in the Transitional Annex XV dossier in 2009. The default UF of 100 was also recently used by the ECHA Committee for Risk Assessment (RAC) in their opinion on new scientific evidence on the use of boric acid and borates in photographic applications by consumers adopted 29 April 2010. However, the default value was used because of insufficient time for an in-depth assessment of the toxicokinetic data. The RAC acknowledged that the 10 x 10 was an overly conservative and that there was good scientific justification to derogate from the default values. Further the RAC recognized the UF of 60 used by WHO in deriving its Guidelines for Drinking Water Quality (2002 & 2009) for boron, and that EFSA in 2004 also utilised a combined UF of 60 (Minutes of the 10th meeting of the Committee for Risk Assessment, 16-18 march 2010).


More recently an UF of 60 was used by the Scientific Committee on Health and Environmental Risks (SCHER) 2010 Derogation on the Drinking Water Directive 98/83/EC for Boron (SCHER 2010), and the Scientific Committee on Consumer Safety (SCCS) 2010 opinion on Boron compounds (SCCS 2010).


The European Centre for Ecotoxicology and Toxicology of Chemicals (ECETOC) is developing guidance on the use of assessment (AF) when deriving DNELs (ECETOC 2010). When substance-specific data documenting intra-species variability are available, the use of ‘informed’ AF, rather than the default AF provided in the ECHA guidance is proposed. Such data can be toxicokinetic or toxicodynamic data, and demonstrate either the absence of variability between humans, or on the contrary indicate that some parts of the population may require additional consideration (e. g. young children, the elderly).


In the absence of substance-specific data, ECETOC guidance is to deviate from the default AF of 10 (general population) and 5 (workers) as recommended by the ECHA R8 and to use default values of 5 and 3, for workers and the general population respectively. These values have been proposed in the ECETOC guidances (2003, 2010).


In the case where allometric scaling is already applied (systemic effects), it is proposed to use an overall additional factor covering the total (inter- and intra-species) variability, of 5 for the general population and 3 for the workplace. In the case where local effects in the respiratory tract are of concern, the intraspecies factors of 5 and 3 are considered to also provide coverage for toxicodynamic differences. This is relevant since compared to rats; humans seem to be less susceptible to the toxic local effects in the respiratory tract associated with inhalation of inorganic metal compounds (Oberdörster, 1995; Mauderly, 1997; ILSI, 2000; Nikula et al., 2001; Greim and Ziegler-Skylakakis, 2007).


The basis provided by ECETOC for the use of the reduced AFs includes:



  • both the ECHA guidance (R8) and ECETOC recognise that, when substance- or category-specific information is available, there may be scientific justification for deviating from default AFs

  • statistical analysis of the variability of toxicodynamic and toxicokinetic parameters within several published datasets has shown that the intra-species variability between humans can be covered by an AF of 5 for the general population and an AF of 3 for the more homogeneous worker population

  • It is anticipated that a low variability in response would be seen in human populations exposed to boric acid that does not undergo extensive metabolism (and have lower genetic polymorphisms) than in populations exposed to substances that required more extensive metabolism.

  • if allometric scaling is used, although some interspecies variability may remain, it is estimated that this residual variability is largely accounted for in the default assessment factor proposed for intra-species variability, because of the inherent interdependency of those two variables. In the case where local effects in the respiratory tract are of concern, the intraspecies factors of 5 and 3 are considered to also provide coverage for toxicodynamic differences.


Although the more conservative AF was used in derivation of the DNEL in this CSR a reevaluation of the appropriate AF to use will be conducted upon final publication of the ECETOC guidelines that may result in a reduction of the AFs as outline by ECETOC guidance.


General population-DNELlong-term, oral, systemic= (10.3 mg B/kg bw/day) / (6 x 10) =0.17 mg B/kg bw/day or: 


Sodium pentaborate (anhydrous): 0.64 mg/kg bw/day


Sodium pentaborate (pentahydrate): 0.93 mg/kg bw/day