Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
irritation (respiratory tract)
Route of original study:
By inhalation
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
irritation (respiratory tract)
Route of original study:
By inhalation
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
25 mg/m³
Most sensitive endpoint:
irritation (respiratory tract)
DNEL related information
DNEL derivation method:
other: ECHA - substance specific AFs
Overall assessment factor (AF):
1
Dose descriptor:
NOAEC
AF for dose response relationship:
1
Justification:
default AF; clear NOAEC
AF for differences in duration of exposure:
1
Justification:
Local effect, not relevant
AF for interspecies differences (allometric scaling):
1
Justification:
ECHA default – human data
AF for other interspecies differences:
1
Justification:
This is consistent with local irritant property induced by an elevated concentration of a strongly acidic substance with little if any difference in toxicodynamic effect across species
AF for intraspecies differences:
1
Justification:
This is consistent with local irritant property induced by an elevated concentration of a strongly acidic substance with little if any difference in toxicodynamic effect within species
AF for the quality of the whole database:
1
Justification:
Default AF (human data available)
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
25 mg/m³
Most sensitive endpoint:
irritation (respiratory tract)
DNEL related information
DNEL derivation method:
other: ECHA - substance specific AFs
Overall assessment factor (AF):
1
DNEL extrapolated from long term DNEL
Dose descriptor starting point:
NOAEC
AF for dose response relationship:
1
Justification:
Local effect, not relevant
AF for interspecies differences (allometric scaling):
1
Justification:
ECHA default – human data
AF for other interspecies differences:
1
Justification:
This is consistent with local irritant property induced by an elevated concentration of a strongly acidic substance with little if any difference in toxicodynamic effect within species
AF for intraspecies differences:
1
Justification:
This is consistent with local irritant property induced by an elevated concentration of a strongly acidic substance with little if any difference in toxicodynamic effect within species
AF for the quality of the whole database:
1
Justification:
Default AF (human data available)
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties

Workers - Hazard via dermal route

Systemic effects

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

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - workers

Since the initial REACH submission in November 2010, acetic acid has been considered by the Scientific Committee on Occupational Exposure Limits and concluded on an 8 hour OEL of 10 ppm (25 mg/m3) and STEL (15-min) of 20 ppm (50 mg/m3) (SCOEL/SUM/98; June 2012). This OEL is an agreement with the DNELl-t localproposed in the original REACH submission with rationale provided below. The proposed DNELacute local is amended to concur with the SCOEL recommendation.

The critical effect of occupational exposure to acetic acid is irritation of the skin and mucous membrane. There is reliable dose-response data on sensory irritation in human volunteers and this can be used to set limits for exposure. Minor subjective irritant effects have been reported in two volunteer studies at 10-ppm exposures (Ernstgård et al 2006, HVBG 2007). Although Ernstgård et al (2006) noted a nonsignificant increase in eye blink frequency at 10 ppm, this response was not observed in the larger study on volunteers observed over 4 hours and reported by HVBG (2007). Neither the Ernstgård nor the HVBG studies observed any physiological changes compatible with irritation at 10-ppm exposures. Ernstgård et al studied 11 volunteers in a 2-hour exposure and HVBG 24 subjects over 4 hours. The results reported in the two studies are comparable. Given the minor subjective effects reported at 10 ppm, the absence of any physiological measurements of irritation at this concentration, the possibility that smell may be affecting some self-reported ratings of irritation by the volunteers and a laterilisation (irritation) threshold of 40 ppm it is possible to recommend an 8-hour OEL of 10 ppm. Assuming 100 % respiratory uptake the inhaled dose over a working shift would be about 250 mg (25 mg/m3 x 10 m3). Given that the daily turnover of the acetate ion (the ionic form of acetic acid) is estimated to be about 45 g/day no systemic effects are expected at the proposed OEL. With an irritation (laterilisation) threshold identified at 40 ppm, it is unlikely that at exposures half of this there will be noticeable irritation over the short term and therefore a 20 ppm STEL can also be recommended.

For the purposes of this submission DNEL values are derived following the principles outlined in the relevant REACH guidance (Chapter R.8: Characterisation of dose [concentration]-response for human health).

Acute toxicity

A DNEL for acute toxicity should be derived if an acute hazard leading to acute toxicity (e.g. C&L) has been identified and there is a potential for high peak exposures. These “peaks” are normally associated with inhalation exposure, but are less common for skin contact and ingestion (Appendix R.8-8).  Acetic acid does not present an acute hazard (i.e. has no CLP classification) following ingestion, inhalation or skin contact. From the acute data it is possible to define a threshold for irritation to establish DN(M)ELs for local effects. 

Local DNEL inhalation

Acute and long-term local DNEL inhalation values are based on human data reported by HVBG (2007) and Kleinbeck (2009)ith a NOAEC of 10 ppm (25 mg/m3).  Discussion of selection of this endpoint for risk characterisation can be found in the irritation endpoint summary.

Dose descriptor

For acute and repeat dose NOAEC – local effects – 10 ppm (25 mg/m3).

Acute and long term – local effects – DNELinhalation= 25 mg/m3

Systemic DNELs

It is not considered relevant to derive a systemic DNELinhal for acetic acid as the critical effects are local and a local DNELinhal of 10 ppm (25 mg/mg3) is proposed.  This DNELinhal is considered protective for systemic effects i.e. systemic dose resulting from inhalation exposure that is tolerable in respect of local effects will always be negligible. The rationale for this is provided below: Considering systemic toxicity, there is no identified hazard as all effects are attributable to local effects at the site of entry (see repeat dose endpoint summary; section 5.5.4 above). Systemic exposure to acetic acid at exposure levels associated with the uses supported in this submission are insignificant compared with average daily intake. Following intake it has been shown that 120 mg/kg bw can be rapidly removed via the citric acid cycle (~0.5 mg/kg bw acetate removed per minute) in human subjects following administration of acetate in a drink (Smith et al., 2007), and daily administration of 40 mg/kg bw/day may be used as a medicinal product (Johnston & Gaas, 2006), and 25 mg/kg bw /day estimated as average human (infant) dietary intake (Ishiwata et al 2002), with peak excursions up to 240 mg/kg bw /day (EU DAR acetic acid, 2008). An atmospheric concentration of 10 ppm (25 mg/m3) acetic acid is the proposed NOAEC for local irritation effects.  For worker systemic exposure at this concentration, for an 8 hour day spent at light work and assuming 100% absorption for a worker would be equivalent to a daily systemic dose of:

= 25 x wRVhuman(8h)           

= 25 x 0.144

= 3.6 mg/kg bw per workday (8 h)

For the general population, systemic exposure at this concentration, for a 24 hour day and assuming 100% absorption would be equivalent to a daily systemic dose of:

= 25 x sRVhuman(24h)

= 25 x 0.288

= 7.2 mg/kg bw/d

Putting these values in perspective, they represent only a fraction of the total acetate which can be rapidly removed via the citric cycle each day and are low compared with human dietary intake.    

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
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:
25 mg/m³
Most sensitive endpoint:
irritation (respiratory tract)
DNEL related information
DNEL derivation method:
other: ECHA - substance specific AFs
Overall assessment factor (AF):
1
Dose descriptor:
NOAEC
AF for dose response relationship:
1
Justification:
default AF; clear NOAEC
AF for differences in duration of exposure:
1
Justification:
Local effect, not relevant
AF for interspecies differences (allometric scaling):
1
Justification:
ECHA default – human data
AF for other interspecies differences:
1
Justification:
This is consistent with local irritant property induced by an elevated concentration of a strongly acidic substance with little if any difference in toxicodynamic effect across species
AF for intraspecies differences:
1
Justification:
This is consistent with local irritant property induced by an elevated concentration of a strongly acidic substance with little if any difference in toxicodynamic effect within species
AF for the quality of the whole database:
1
Justification:
Default AF (human data available)
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
25 mg/m³
Most sensitive endpoint:
irritation (respiratory tract)
DNEL related information
Overall assessment factor (AF):
1
Dose descriptor starting point:
NOAEC
AF for dose response relationship:
1
Justification:
default AF; clear NOAEC
AF for interspecies differences (allometric scaling):
1
Justification:
Local effect, not relevant
AF for other interspecies differences:
1
Justification:
ECHA default – human data
AF for intraspecies differences:
1
Justification:
This is consistent with local irritant property induced by an elevated concentration of a strongly acidic substance with little if any difference in toxicodynamic effect within spec
AF for the quality of the whole database:
1
Justification:
Default AF (human data available)
AF for remaining uncertainties:
1
Justification:
No remaining uncetainties

General Population - Hazard via dermal route

Systemic effects

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

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)

General Population - Hazard via oral route

Systemic effects

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

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - General Population

See discussion above