Reaction products of Soya and Linseed Oil Fatty Acids with Bisphenol A diglycidylether

Endpoint summary

Link to relevant study record(s)

Reference

Endpoint:

basic toxicokinetics in vivo

Type of information:

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

Adequacy of study:

key study

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH
This read-across hypothesis corresponds to scenario 2 of the Read-Across Assessment Framework (RAAF), ECHA, March 2017 - different compounds have qualitatively similar properties - of the read-across assessment framework i.e. properties of the target substance are predicted to be quantitatively equal to those of the source substance. Namely, the source substance BADGE predicts the toxicological and ecotoxicological properties of the target substance Soya/Linseed Oil Fatty Acid-BADGE reaction product.

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
for details see Justification for read-across attached to iuclid section 13

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
for details see Justification for read-across attached to iuclid section 13

3. ANALOGUE APPROACH JUSTIFICATION
for details see Justification for read-across attached to iuclid section 13

4. DATA MATRIX
for details see Justification for read-across attached to iuclid section 13

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across: supporting information

Objective of study:

other: Distribution/elimination and metabolism following a single oral or dermal dose.

Duration and frequency of treatment / exposure:

single oral or dermal dose

Details on absorption:

Dermal absorption. When 14C-DGEBPA was applied to the shaved dorsal area of mice (56 mg/kg body wt), daily elimination of radioactivity in the urine rose to a maximum of only 1.3% dose two days after treatment. During the remaining six days of the experiment the daily excretion of radioactivity slowly fell to 0.3% of dose. A similar pattern of elimination was observed for feces. Daily excretion of radioactivity rose to a broad maximum of approximately 8% two and three days after the dermal application, falling to 2.3% of the dose after eight days. A relatively large proportion of the administered dose could be extracted from the skins of the mice one (67%), three (41%) and eight (11%) days after treatment. Additionally, a mean figure of 26% of the administered dose could be recovered by washing the foil, covering the application area, with methanol. The radioactivity recovered in this manner, remained approximately constant throughout the experiment.
The methanol-acetone extract of the skin was analyzed by TLC. One day after treatment 97% of the extractable radioactivity on the skin was DGEBPA; 3% was unidentified polar material. After eight days the corresponding figures were 81% and 19% of the extractable activity respectively. After methanol-aceone extraction, the skin was further extracted with methanol-water to yield 0.1% dose and finally with 3M HCl to give 0.2% dose. Samples of the extracted skin were combusted and the results showed that the amount of 14C chemically bound to the skin increased from 0.3% dose after one day, to 0.5% after three days and to 1.8% dose after eight days.
The toal recovery of radioactivity including cage washings was 95%.

Oral dosing. When 14C-DGEBPA was dosed orally to mice (~55 mg/kg), radioactivity was eliminated mostly in the feces (~80%) and to a lesser extent in the urine (~11%) over the first three days of the experiment. Excretion was very rapid, being over 88% of the administered dose within two days. The tissue radioactivity rapidly depleted from all the tissues studied during the course of the eight day experiment. The total recovery of radioactivity, including cage washings, was 93%.

Details on distribution in tissues:

The level of radioactivity remaining in the animals eight days after treatment was 0.74% of the administered dose excluding the figure for the skin. Most of this activity was located in the intestines of the animals (0.55% of dose, mean figure from the two animals).

Details on excretion:

Dermally-applied BADGE (56 mg/kg) to mice was slowly eliminated in the feces (20% of dose) and urine (3%) as a mixture of metabolites, over three days. Another 20 % was excreted in the feces and 2% in the urine between days 3 and 8 after application of test material to the skin. Most of the applied radioactivity (66%) was extracted from the application area and its covering foil.

When BADGE was given orally to mice, it was rapidly excreted; 80% in the feces and 11% in the urine 0-3 days following a single oral dose. Over 88% of the administered dose was eliminated within 2 days. The tissue radioactivity rapidly depleted from all the tissues studies during the course of the eight day experiment. The total recovery of radioactivity, including cage washings, was 93%.

Metabolites identified:

yes

Details on metabolites:

The urinary and fecal metabolite profiles derived from dermal application and oral dosing were essentially similar. The major metabolic transformation is by hydrolytic ring-opening of the two epoxide rings to form diols. This metabolite (the bis-diol of BADGE) is excreted in both free and conjugated forms and is further metabolized to various carboxylic acids, including two containing a methylsulphonyl moiety in amounts representing about 5% of the dose. The high activity of epoxide hydratase towards BADGE suggests that glyceraldehyde and not glycidaldehyde is formed in vivo.

Conclusions:

Dermally applied BADGE to mice was only slowly eliminated in the feces (20% of dose) and urine (3%) as a mixture of metabolites, over three days. When BADGE was given orally to mice, it was rapidly excreted; 80% in the feces and 11% in the urine 0-3 days following a single oral dose. The urinary and fecal metabolite profiles derived from dermal application and oral dosing were essentially similar. The major metabolic transformation is by hydrolytic ring-opening of the two epoxide rings to form diols. This metabolite (the bis-diol of BADGE) is excreted in both free and conjugated forms and is further metabolized to various carboxylic acids, including two containing a methylsulphonyl moiety in amounts representing about 5% of the dose. The high activity of epoxide hydratase towards BADGE suggests that glyceraldehyde and not glycidaldehyde is formed in vivo. No bisphenol A was formed following treatment of mice with BADGE.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Absorption rate - oral (%):

50

Absorption rate - dermal (%):

50

Absorption rate - inhalation (%):

100